Iron deficiency,but not underfeeding reduces the secretion of interferon-gamma by mitogen-activated murine spleen cells

Interferon-gamma (IFN-γ), a cytokine primarily secreted by T and natural killer cells regulates cell-mediated and innate immunity. Iron deficiency, a public health problem in children impairs immune function. To determine whether reduced IFN-γ contributes to impaired immunity, we measured IFN-γ in supernatants of activated (2.5 μg/ml concanavalin A, 50 ng/ml anti-CD3 antibody) spleen cells from control (C), iron-deficient (ID), pair-fed (PF), and iron-replete mice for 3 (R3) and 14 days (R14) (11–12/group). Except for iron content, the low iron (5 ppm) and control (50 ppm) diets had identical composition. Mean indices of iron status after 51 days of feeding were as follows: C = PF ≈ R14 > R3 > ID (p < 0.01). Iron deficiency, but not pairfeeding reduced IFN-γ concentration in mitogen-treated cells by 30–43% (p < 0.05); iron repletion improved it. Reduced IFN-γ was not simply due to differences in IL-12 (IFN-γ inducer), percentage of CD3+ T cells, or impaired cell proliferation because these indices were not always decreased. It was likely due to a defect in T cell activation that leads to IFN-γ gene expression. IFN-γ positively correlated with indicators of iron status, body, and thymus weights (r = 0.238–0.472; p < 0.05). Reduced IFN-γ secretion during iron deficiency may affect response to infections.     

The roles of aerobic exercise training and suppression IL-6 gene expression by RNA interference in the development of insulin resistance

ObjectiveTo demonstrate the hypothesis that aerobic exercise training inhibits the development of insulin resistance through IL-6 and probe into the possible molecular mechanism about it.MethodsRats were raised with high-fat diets for 8 weeks to develop insulin resistance, and glucose infusion rates (GIRs) were determined by hyperinsulinemic–euglycemic clamping to confirm the development of insulin resistance. Aerobic exercise training (the speed and duration time in the first week were respectively 16 m/min and 50 min, and speed increased 1 m/min and duration time increased 5 min every week following it) and/or IL-6shRNA plasmid injection (rats received IL-6shRNA injection via the tail vein every two weeks) were adopted during the development of insulin resistance. The serum IL-6, leptin, adiponectin, fasting blood glucose, fasting serum insulin, GIR, IL-6 gene expression levels, p-p38 in various tissues and p-STAT3/t-STAT3 ratio in the liver were measured.ResultsRats fed with high-fat diets for 8 weeks were developed insulin resistance and the IL-6mRNA levels of IL-6shRNA injection groups in various tissues were significantly lower than those of control group (P < 0.05), respectively. The development of insulin resistance in exercise rats significantly decreased, however, compared with that, the GIR of exercise rats injected by IL-6shRNA was lower (P < 0.05). The IL-6mRNA levels were highest in the fat tissue and lowest in the skeletal muscles in all the rats. The serum adiponectin levels decreased (P < 0.05) following the development of insulin resistance, and it increased (P < 0.05) when the rats were intervened by aerobic exercise training for 8 weeks at the same time. However, there were not significant differences when serum leptin concentrations were compared (P > 0.05). The p-p38 significantly increased in the rats fed with high-fat diets, however, p-p38 of the exercise high-fat diets rats in the liver and fat tissues significantly decreased than that (P < 0.05). The changes of p-p38 in exercise rats injected by IL-6shRNA were irregular. The activation of STAT3 in the liver significantly increased (P < 0.05) following the development of insulin resistance, and it decreased (P < 0.05) when the rats were intervened by aerobic exercise training for 8 weeks at the same time, and the gene silencing of IL-6 did not have effects on the activation of STAT3 in the liver (P > 0.05).ConclusionsIn conclusion, aerobic exercise training prevented the development of insulin resistance through IL-6 to a certain degree. The gene expression and secretion of IL-6 could inhibit the development of insulin resistance. The mechanism of the effects were possibly related with elevating the levels of serum adiponectin, and/or inhibiting the activation of STAT3 in the liver and p38MAPK in the skeletal muscles, liver and fat tissues.     

Tri-axial accelerometer analysis techniques for evaluating functional use of the extremities

Activity monitors provide an objective mechanism for evaluating patient function. It is unclear what similarities or unique information may be yielded using different analyses. Fifteen patients scheduled to undergo shoulder arthroplasty and fifteen matched control subjects wore tri-axial accelerometer activity monitors bilaterally at the lower (wrist) and upper (biceps) arm for 3 days. Measures of central tendency, variance, sample entropy, and asymmetry were calculated. A novel technique to evaluate time distribution of activity intensity was also performed. Within both groups there was a difference in central tendency and variance when comparing dominant and non-dominant limbs for both the lower (Controls: Mean Activity, P < 0.001; Max Activity, P < 0.001; Patients: Mean Activity, P = 0.044; Max Activity, P = 0.009) and upper (Controls: Mean Activity, P < 0.001; Max Activity, P = 0.046; Patients: Mean Activity, P = 0.002; Max Activity, P = 0.049) arm. Within group differences were also present for lower arm entropy in both groups (Controls, P < 0.001; Patients P = 0.041), and at the upper arm for patients (P = 0.003). There were differences between groups for the asymmetry index for both the lower (P = 0.033) and upper arm (P = 0.005), and maximum activity level of the lower arm (P = 0.05). Between group differences were present for time distribution of activity intensity, as the involved upper arm of patients was inactive for a greater time than controls (P = 0.013). These results highlight unique information provided by multiple analysis methods, and include a novel approach of evaluating the distribution of time spent across variable intensity activities.     

Pregnancy and maternal iron deficiency stimulate hepatic CRBPII expression in rats

Iron deficiency impairs vitamin A (VA) metabolism in the rat but the mechanisms involved are unknown and the effect during development has not been investigated. We investigated the effect of pregnancy and maternal iron deficiency on VA metabolism in the mother and fetus. 54 rats were fed either a control or iron deficient diet for 2 weeks prior to mating and throughout pregnancy. Another 15 female rats followed the same diet and were used as non-pregnant controls. Maternal liver, placenta and fetal liver were collected at d21 for total VA, retinol and retinyl ester (RE) measurement and VA metabolic gene expression analysis. Iron deficiency increased maternal hepatic RE (P < .05) and total VA (P < .0001), fetal liver RE (P < .05), and decreased placenta total VA (P < .05). Pregnancy increased Cellular Retinol Binding Protein (CRBP)-II gene expression by 7 fold (P = .001), decreased VA levels (P = .0004) and VA metabolic gene expression (P < .0001) in the liver. Iron deficiency increased hepatic CRBPII expression by a further 2 fold (P = .044) and RBP4 by ~ 20% (P = .005), increased RBPR2 and decreased CRBPII, LRAT, and TTR in fetal liver, while it had no effect on VA metabolic gene expression in the placenta. Hepatic CRBPII expression is increased by pregnancy and further increased by iron deficiency, which may play an important role in VA metabolism and homeostasis. Maternal iron deficiency also alters VA metabolism in the fetus, which is likely to have consequences for development.     

Severe preeclampsia: Association of genes polymorphisms and maternal cytokines production in Brazilian population

IntroductionPreeclampsia (PE) is a multi-system disorder of pregnancy characterized by hypertension and proteinuria. Healthy pregnancy is associated with a controlled inflammatory process, which is exacerbated in PE in response to excessive placental stimuli. Gene expression levels can affect inflammation and immune regulation. It is known that differences in cytokine allele frequencies amongst populations may contribute to difference in the incidence of several diseases.ObjectiveThe aim of this study was to investigate the frequency of TNF-α, IL-6, IFN-γ and IL-10 genes polymorphisms and their relationship with the cytokines plasma levels in PE.MethodsA total of 281 women were included in this study; 116 with severe PE, 107 normotensive pregnant and 58 non-pregnant women. Cytokine genotyping was carried out by the polymerase chain reaction. The analyzed polymorphisms were: TNF-α (−308 G → A), IL-10 (−1082 G → A), IL-6 (−174 G → C), and IFN-γ (+874 A → T). Cytokine plasma levels were measured by Cytometric Bead Array method.ResultsA higher frequency of the IFN-γ (+874) T/T genotype in severe PE comparing to normotensive pregnant women was found (P < 0.001). TNF-α, IL-6 and IFN-γ plasma levels were higher in PE women compared to non-pregnant women (P < 0.001; P < 0.001; P = 0.004). IL-6 and IFN-γ levels were also higher in PE women compared to normotensive pregnant (P < 0.001; P = 0.010). IL-10 levels were higher in normotensive pregnant women compared to PE (P < 0.001). IFN-γ and IL-6 genes polymorphisms influenced the genic expression in PE and normotensive pregnant women, respectively.ConclusionsThese results suggest that IFN-γ seems to play a role in PE occurrence.     

Transforming growth factor-β and Th17 responses in resistance to primary murine schistosomiasis mansoni

Discovery of the T-helper (Th) 17 cell lineage and functions in immune responses of mouse and man prompted us to investigate the role of transforming growth factor-beta (TGF-β) and interleukin (IL)-17 in innate resistance to murine schistosomiasis mansoni. Schistosoma mansoni-infected BALB/c and C57BL/6 mice were administered with recombinant TGF-β or mouse monoclonal antibody to TGF-β to evaluate the impact of this cytokine on host immune responses against lung-stage schistosomula, and subsequent effects on adult worm parameters. Developing schistosomula elicited increase in peripheral blood mononuclear cells (PBMC) mRNA expression and/or plasma levels of IL-4, IL-17, and interferon-gamma (IFN-γ), cytokines known to antagonize each other, resulting in impaired Th1/Th2, and Th17 immune responses and parasite evasion. Mice treated with TGF-β showed elevated PBMC mRNA expression of IL-6, IL-17, TGF-β, and TNF-α mRNA and increased IL-23 and IL-17 or TGF-β plasma levels, associated with significantly (P < 0.02–<0.0001) lower S. mansoni adult worm burden compared to controls in both mouse strains, thus suggesting that TGF-β led to heightened Th17 responses that mediated resistance to the infection. Mice treated with antibody to TGF-β showed increase in PBMC mRNA expression and plasma levels of IL-4, IL-12p70, and IFN-γ, and significantly (P < 0.02 and <0.0001) reduced worm burden and liver worm egg counts than untreated mice, indicating that Th1/Th2 immune responses were potentiated, resulting in significant innate resistance to schistosomiasis. The implications of these observations for schistosome immune evasion and vaccination were discussed.     

Activation of foal neutrophils at different ages by CpG oligodeoxynucleotides and Rhodococcus equi

Toll-like receptor 9 (TLR9) activation stimulates protective immune responses against intracellular pathogens by phagocytes, including neutrophils. This study examined TLR9-mediated neutrophil activation in neonatal foals. Unmethylated CpGs, ligands for TLR9, were used to stimulate equine neutrophils, either purified or in contact with other peripheral blood leukocytes. Rhodococcus equi was used as another stimulus in parallel. TLR9 mRNA was constitutively expressed at a similar level in purified equine neutrophils across different ages from birth to adulthood, and expression was not affected by either CpG or R. equi. Purified foal neutrophils were directly sensitive to CpG stimulation, reflected by enhanced reactive oxygen species generation following fMLP stimulation, and by expressing significantly (P < 0.05) greater mRNA of IFN-γ, IL-8, IL-12p35, and significantly (P < 0.05) decreased TNF-α mRNA. In comparison, purified foal neutrophils stimulated by R. equi showed significantly (P < 0.05) increased mRNA production of IL-6, IL-8, IL-23p19, and TNF-α. Neutrophils co-cultured with other leukocytes expressed a distinct profile of cytokine mRNA than purified neutrophils in response to CpG stimulation, whereas the profile was very similar following R. equi stimulation irrespective of neutrophil purity. When co-cultured with other leukocytes, foal neutrophils were significantly (P < 0.05) activated at birth by B-class CpGs and produced IL-6, IL-8, IL-12p40, and IL-23p19 at similar magnitudes to those at 2 months of age. In foal neutrophils at birth, R. equi significantly (P < 0.05) induced all cytokines stimulated by CpGs (except IL-12p40), as well as TNF-α. Our results indicate that foal neutrophils were sensitive to CpG or R. equi activation as early as at birth, and that B-class CpGs enhanced foal neutrophil functions in vitro.     

Vasoactive intestinal peptide (VIP) differentially affects inflammatory immune responses in human monocytes infected with viable Salmonella or stimulated with LPS

We compared the effect of VIP on human blood monocytes infected with Salmonella typhimurium 4/74 or stimulated with LPS. VIP (10⁻⁷ M) increased monocyte viability by 24% and 9% when cultured for 24 h with 4/74 or Salmonella LPS (100 ng/ml), respectively. Significantly increased (P < 0.05) numbers of 4/74 were also recovered from monocytes co-cultured with VIP after 6 h post-infection (pi) and this remained high after 24 h pi. Both 4/74 and LPS increased (P < 0.05) the concentration of TNF-α, IL-1β and IL-6 measured in monocyte supernatants. However, LPS induced this effect more rapidly while, with the exception of IL-6, 4/74 induced higher concentrations (P < 0.05). VIP significantly decreased (P < 0.05) TNF-α and IL-1β production by 4/74-infected monocytes after 6 pi, but only after 24 h in LPS-cultured monocytes. This trend was reversed for IL-6 production. However, TNF-α and IL-1β production by 4/74-infected monocytes, cultured with VIP, still remained higher (P < 0.05) than concentrations measured in supernatants cultured only with LPS. VIP also increased (P < 0.05) production of anti-inflammatory IL-10 in both 4/74 and LPS cultures after 24 h. We also show a differential effect of VIP on the expression of TNFα and IL-6 receptors, since VIP was only able to decreased expression in LPS-stimulated monocytes but not in 4/74-infected monocytes.In conclusion, we show a differential effect of VIP on human monocytes infected with virulent Salmonella or stimulated with LPS. Our study suggests that the use of VIP in bacteraemia and/or sepsis may be limited to an adjunctive therapy to antibiotic treatment.     

Impairment of the non-homologous end joining and homologous recombination pathways of DNA double strand break repair: Impact on spontaneous and radiation-induced mammary and intestinal tumour risk in Apcmin/+ mice

Female Apc^min/+ mice carrying the BALB/c variant of Prkdc or heterozygous knockout for Xrcc2, were sham- or 2 Gy X-irradiated as adults to compare the effect of mild impairments of double–strand break (DSB) repair pathways, non-homologous end joining (NHEJ) and homologous recombination (HR) respectively on spontaneous and radiation–induced mammary and intestinal tumorigenesis. Mice with impaired NHEJ showed no difference in incidence of spontaneous mammary tumours, compared with matched controls, (2.46 fold, P = 0.121) and significantly less following irradiation (radiation–induced excess; 0.35 fold, P = 0.008). In contrast mice with impaired HR presented with significantly less spontaneous mammary tumours than matched controls (0.33 fold, P = 0.027) and significantly more following irradiation (radiation-induced excess; 3.3 fold, P = 0.016). Spontaneous and radiation-induced intestinal adenoma multiplicity in the same groups were significantly greater than matched controls for mice with impaired NHEJ (sham; 1.29 fold, P < 0.001, radiation–induced excess; 2.55 fold, P < 0.001) and mice with impaired HR showed no significant differences (sham; 0.92 fold, P = 0.166, radiation-induced excess; 1.16, P = 0.274). Genetic insertion events were common in spontaneous tumours from NHEJ impaired mice compared with matched controls. γH2AX foci analysis suggests a significantly faster rate of DSB repair (MANOVA P < 0.001) in intestinal than mammary tissue; apoptosis was also higher in irradiated intestine.To conclude, results suggest that pathway of choice for repair of spontaneous and radiation-induced DSBs is influenced by tissue type. NHEJ appears to play a greater role in DSB repair in intestinal tissue since impairment by functional change of Prkdc significantly increases the rate of mis-repair in intestinal but not mammary tissue. HR appears to play a greater role in DSB repair in adult mammary tissue since impaired HR results in significant changes in mammary but not in the intestinal tumorigenesis. This indicates that early DNA damage response and repair is important for cancer susceptibility and plays a role in determining tissue specificity of cancer risk.     

Cytokine expression profile over time in burned mice

The persistent inflammatory response induced by a severe burn increases patient susceptibility to infections and sepsis, potentially leading to multi-organ failure and death. In order to use murine models to develop interventions that modulate the post-burn inflammatory response, the response in mice and the similarities to the human response must first be determined. Here, we present the temporal serum cytokine expression profiles in burned mice in comparison to sham mice and human burn patients. Male C57BL/6 mice were randomized to control (n = 47) or subjected to a 35% TBSA scald burn (n = 89). Mice were sacrificed 3, 6, 9, 12, 24, and 48 h and 7, 10, and 14 days post-burn; cytokines were measured by multi-plex array. Following the burn injury, IL-6, IL-1β, KC, G-CSF, TNF, IL-17, MIP-1α, RANTES, and GM-CSF were increased, p < 0.05. IL-2, IL-3, and IL-5 were decreased, p < 0.05. IL-10, IFN-γ, and IL-12p70 were expressed in a biphasic manner, p < 0.05. This temporal cytokine expression pattern elucidates the pathogenesis of the inflammatory response in burned mice. Expression of 11 cytokines were similar in mice and children, returning to lowest levels by post-burn day 14, confirming the utility of the burned mouse model for development of therapeutic interventions to attenuate the post-burn inflammatory response.     

The relationship between interleukin-6 in saliva,venous and capillary plasma,at rest and in response to exercise

IL-6 plays a mechanistic role in conditions such as metabolic syndrome, chronic fatigue syndrome and clinical depression and also plays a major role in inflammatory and immune responses to exercise. The purpose of this study was to investigate the levels of resting and post exercise IL-6 when measured in venous plasma, saliva and capillary plasma. Five male and five females completed 2 separate exercise trials, both of which involved standardized exercise sessions on a cycle ergometer. Venous blood and saliva samples were taken immediately before and after Trial A, venous and capillary blood samples were taken immediately before and after Trial B. IL-6 values were obtained using a high-sensitivity enzyme-linked immunosorbent assay (ELISA). In Trial A venous plasma IL-6 increased significantly from 0.4 ± 0.14 pg/ml to 0.99 ± 0.29 pg/ml (P < 0.01) while there was no increase in salivary IL-6. Venous plasma and salivary IL-6 responses were not correlated at rest, post exercise or when expressed as an exercise induced change. In Trial B venous and capillary plasma IL-6 increased significantly (venous: 0.22 ± 0.18 to 0.74 ± 0.28 pg/ml (P ⩽ 0.01); capillary: 0.37 ± 0.22 to 1.08 ± 0.30 pg/ml (P < 0.01). Venous and capillary plasma responses did not correlate at rest (r = 0.59, P = 0.07) but did correlate post exercise (r = 0.79, P ⩾ 0.001) and when expressed as an exercise induced change (r = 0.71, P = 0.02). Saliva does not appear to reflect systemic IL-6 responses, either at rest or in response to exercise. Conversely, capillary plasma responses are reflective of systemic IL-6 responses to exercise.     

Clinical profile of sheep fed non-conventional feeds containing phenols and condensed tannins

A study was carried out to investigate the effects of feeding low quality non-conventional feeds (NCF) containing phenols and condensed tannins on the clinical profiles of sheep. Thirty-two Omani sheep were fed one of four diets with two base roughages, urea-treated palm frond (UTPF) and Rhodesgrass hay (RGH) and two concentrates, commercial concentrate (CC) and a by-products concentrate (BC) for 120 days. Haematological, serum biochemical and urine analyses were used to assess sheep health. Non-conventional feeds (urea-treated palm frond and by-products concentrate) contained higher levels of polyphenols and condensed tannins than conventional feeds (Rhodesgrass hay and commercial cubes). Feeds based on urea-treated palm frond had lower dry matter, crude protein, acid detergent fibre, neutral detergent fibre, gross energy (P < 0.001) and ash (P < 0.05) digestibility coefficients than those based on Rhodesgrass hay. Animals fed NCF had lower feed intake (P < 0.001) and lower body gain (P < 0.001) than those fed conventional ones. They also produced larger volumes of faeces (P < 0.01) which contained higher levels of nitrogen (P < 0.001) and had lower viscosity values of intestinal content (P < 0.001). Rumen liquor of NCF-fed animals had higher pH and lower ammonia–nitrogen levels (P < 0.01). Animals fed urea-treated palm frond plus by-products concentrate had lower lymphocyte (P < 0.01), monocyte (P < 0.05) and eosinophil (P < 0.05) counts by the end of the trial than those fed Rhodesgrass hay based diets. The urea-treated palm frond and by-products concentrate fed animals had lower blood urea nitrogen (BUN) levels (P < 0.05), higher (P < 0.01) alanine aminotransferase (ALT) and lower serum iron (P < 0.001) than those fed Rhodesgrass hay based diets. There was a trend of increasing blood, leukocytes and specific gravity in the urine of NCF-fed animals. This experiment implies that feeding low quality non-conventional feeds containing antinutritional factors for relatively long periods might produce subtle negative effects on the physiology and chemistry of the digestive system and blood parameters which might negatively affect sheep health and make them more susceptible to diseases.     

Cathepsin G activity lowers plasma LDL and reduces atherosclerosis

Cathepsin G (CatG), a serine protease present in mast cells and neutrophils, can produce angiotensin-II (Ang-II) and degrade elastin. Here we demonstrate increased CatG expression in smooth muscle cells (SMCs), endothelial cells (ECs), macrophages, and T cells from human atherosclerotic lesions. In low-density lipoprotein (LDL) receptor-deficient (Ldlr^–/–) mice, the absence of CatG reduces arterial wall elastin degradation and attenuates early atherosclerosis when mice consume a Western diet for 3 months. When mice consume this diet for 6 months, however, CatG deficiency exacerbates atherosclerosis in aortic arch without affecting lesion inflammatory cell content or extracellular matrix accumulation, but raises plasma total cholesterol and LDL levels without affecting high-density lipoprotein (HDL) or triglyceride levels. Patients with atherosclerosis also have significantly reduced plasma CatG levels that correlate inversely with total cholesterol (r = –0.535, P < 0.0001) and LDL cholesterol (r = –0.559, P < 0.0001), but not with HDL cholesterol (P = 0.901) or triglycerides (P = 0.186). Such inverse correlations with total cholesterol (r = –0.504, P < 0.0001) and LDL cholesterol (r = –0.502, P < 0.0001) remain significant after adjusting for lipid lowering treatments among this patient population. Human CatG degrades purified human LDL, but not HDL. This study suggests that CatG promotes early atherogenesis through its elastinolytic activity, but suppresses late progression of atherosclerosis by degrading LDL without affecting HDL or triglycerides.     

An immunomodulatory peptide related to frenatin 2 from skin secretions of the Tyrrhenian painted frog Discoglossus sardus (Alytidae)

Norepinephrine-stimulated skin secretions of the Tyrrhenian painted frog Discoglossus sardus Tschudi, 1837 (Alytidae) did not contain any peptide with antimicrobial or hemolytic activity. However, peptidomic analysis of the secretions revealed the presence of an abundant peptide with structural similarity to frenatin 2, previously isolated from the Australian frog Litoria infrafrenata (Hylidae). The primary structure of the peptide, termed frenatin 2D, was established as DLLGTLGNLPLPFI.NH₂ by automated Edman degradation and mass spectrometry with electron-transfer dissociation (ETD)-based fragmentation and confirmed by chemical synthesis. The structure of a second frenatin 2-related peptide, termed frenatin 2.1D, that was present in much lower abundance was established as GTLGNLPAPFPG. Frenatin 2D (20 μg/ml) significantly stimulated production of the proinflammatory cytokines TNF-α (P < 0.05) and IL-1β (P < 0.01) by mouse peritoneal macrophages but the peptide did not potentiate the stimulation produced by lipopolysaccharide (LPS). The peptide increased IL-12 production in both unstimulated (P < 0.01) and LPS-stimulated (P < 0.05) cells but stimulatory effects on IL-6 production were not significant. The biological role of frenatin 2D is unknown but it is speculated that the peptide acts on skin macrophages to produce a cytokine-mediated stimulation of the adaptive immune system in response to invasion by microorganisms.     

Proinflammatory,anti-inflammatory cytokines and adiponkines in students with central obesity

Several studies have investigated the correlation between central obesity and inflammatory cytokines and the anti-inflammatory cytokine adiponectin. But, the correlation between central obesity and the anti-inflammatory cytokines IL-4, IL-5 has not been studied yet. Thus, we aimed to study the IL-4 and IL-5 correlation to central obesity in adolescent Egyptian girls among proinflammatory and anti-inflammatory cytokines. The study was carried out on 86 obese adolescent girls (BMI > 95 percentile) divided into two groups according to central obesity. The group I with waist to hip ratio <0.8 as a control and group II with waist to hip ratio >0.8 (central obesity). There was a significant increase in TNF-alpha (p < 0.0001), and IL-1β (p < 0.0001), as proinflammatory cytokines in group II, as compared to their corresponding group I. Group II showed a significant increase in the anti-inflammatory cytokines IL-4 and IL-5 than group I at (p < 0.0001) and (p < 0.0005) respectively. In addition there was a significant decrease in the anti-inflammatory adiponectin and an increase in the inflammatory leptin levels in group II at (p < 0.0001) and (p < 0.0001) respectively in comparison to group I. A high positive correlation has been observed between waist to hip ratio, leptin, TNF-α, IL-1-β, IL-4 and IL-5 at (r = 0.331, p < 0.03), (r = 0.559, p < 0.001), (r = 0.435, p < 0.004), (r = 0.509, p < 0.001), (r = 0.550, p < 0.0015), in group II respectively and a high negative one with adiponectin at (r = ?0.410, p < 0.0001). We concluded that central obesity lowers adiponectin plasma level through increasing proinflammatory adipokines such as TNF-α, IL-1β, leptin. Further studies are needed to explore the positive correlation we found between central obesity and the anti-inflammatory cytokines IL-4 and IL-5 known to be associated with bronchial asthma.     

Th1/Th2/Th17/Treg cytokine imbalance in systemic lupus erythematosus (SLE) patients: Correlation with disease activity

AimImbalance of T-helper-cell (TH) subsets (TH1/TH2/TH17) and regulatory T-cells (Tregs) is suggested to contribute to the pathogenesis of Systemic lupus erythematosus (SLE). Therefore, we evaluated their cytokine secretion profile in SLE patients and their possible association with disease activity.MethodsSixty SLE patients, 24 rheumatoid arthritis (RA) patients and 24 healthy volunteers were included in this study. Demographic, clinical, disease activity and serological data were prospectively assessed. Plasma cytokines levels of TH1 (IL-12, IFN-γ), TH2 (IL-4, IL-6, IL-10), TH17 (IL-17, IL-23) and Treg (IL-10 and TGF-β) were measured by enzyme linked immunosorbent assays (ELISA).ResultsSLE patients were found to have significantly higher levels of IL-17 (p < 0.001), IL-6 (p < 0.01), IL-12 (p < 0.001) and IL-10 (p < 0.05) but comparable levels of IL-23 and IL-4 and slight reduction (but statistically insignificant) of TGF-β levels compared to controls. IL-6, IL-10 and IL-17 were significantly increased (p < 0.05) with disease activity. The RA group exhibited significantly higher levels of plasma IL-4 (p < 0.01), IL-6 (p < 0.05), IL-17 (p < 0.001), IL-23 (p < 0.01) and TGF-β (p < 0.5) and lower IFN-γ (p < 0.001) and IL-10 (p < 0.01) than those of healthy subjects.ConclusionOur study showed a distinct profile of cytokine imbalance in SLE patients. Reduction in IFN-γ (TH1) and TGF-β1 (Treg) with the elevation in IL-6 and IL-17 (TH17) could imply skewing of T-cells toward TH17 cells. Breaking TH17/Treg balance in peripheral blood may play an important role in the development of SLE and could be responsible for an increased pro-inflammatory response especially in the active form of the disease.     

Genotoxicity assessment in iron deficiency anemia patients using sister chromatid exchanges and chromosomal aberrations assays

Previous studies have shown that iron deficiency anemia is associated with oxidative stress produced by a decrease in antioxidant enzyme activities and/or a high level of oxidants. Because oxidative stress induces DNA damage, we investigated genotoxicity in lymphocytes from patients with iron deficiency anemia (IDA) using chromosomal aberrations (CAs) and sister chromatid exchanges (SCEs) assays. Eighteen IDA subjects and a similar number of age-matched healthy controls were included in the study. The results demonstrated that IDA was associated with a slight increase in the frequency of spontaneous CAs and a decrease in the frequency of SCEs (P < 0.05). In addition, the level of SCEs was positively correlated with both the ferritin concentration (r = 0.485, P < 0.05) and hemoglobin content (r = 0.514, P < 0.05) in subjects. Moreover, vitamin E treatment reduced the frequency of SCEs in IDA patients and control subjects by the same percentage (～30%) without affecting the magnitude of the difference in the levels of SCEs between the two groups. In conclusion, our results demonstrated that IDA has a differential effect on the frequency of spontaneous CAs and SCEs.     

Growth performance and carcass traits of forage-fed hair sheep wethers

The objective of the present study was to compare live animal performance and carcass characteristics of 3/4 or 7/8 Dorper (DO; n = 30), purebred Katahdin (KA; n = 20), purebred St. Croix (SC; n = 17) and purebred Suffolk (SU; n = 10) lambs born in the spring and fall of 2001. After weaning, lambs were supplemented with up to 680 g of a corn-soybean meal supplement while grazing bermudagrass pastures overseeded with ryegrass. Lambs were slaughtered at approximately 210 d of age. From birth to weaning, DO lambs gained faster (P < 0.001) than KA or SC lambs, whereas KA lambs had higher (P < 0.001) ADG than SC lambs. Additionally, DO and SU wethers had greater (P < 0.02) ADG from weaning to slaughter than SC or KA wethers. Suffolk lambs were heavier (P < 0.001) at slaughter and produced heavier (P < 0.001) carcasses than lambs from hair-sheep breeds. Carcasses of KA lambs were fatter (actual fat thickness; P < 0.02) resulting in higher yield grades (P < 0.03) than carcasses of DO, SC, or SU lambs. Carcasses of DO and SU had larger (P < 0.001) longissimus muscle (LM) areas than those of KA or SC carcasses, whereas kidney fat weight and percentage were greater (P < 0.001) in carcasses from KA and SC than DO and SU lambs. Lean maturity was similar (P = 0.32) among breed-types. However, skeletal maturity was greater (P < 0.001) in SU than hair-sheep carcasses. Flank-streaking scores were similar (P = 0.19) among the breed-types, but conformation scores were higher (P < 0.001) for DO and SU carcasses and resulted in higher (P < 0.001) quality grades than SC carcasses. The LM of SU lambs was lighter (higher L^* values; P < 0.05) than that of KA and SC lambs, whereas the LM from DO lambs was redder (higher a^* values; P < 0.001) than SC and SU and more (P < 0.001) yellow than that of the other breed-types. Chops from SU lambs were tougher (higher shear force values; P < 0.007) than chops from the hair-sheep breeds. Results of this study indicate that ADG, carcass muscularity and meat quality were similar between DO and SU lambs, and, although fatter, carcass muscularity of KA was similar to that of DO lambs.     

Immunotherapeutic effects of chitin in comparison with chitosan against Leishmania major infection

Chitin and chitosan microparticles (MPs) are important immune system stimulators. The aim of this study was to evaluate the protective effects of these compounds in comparison with each other against Leishmania infection in BALB/c mice infected with Leishmania major (L. major).Female BALB/c mice were injected subcutaneously with 2 × 10⁵ promastigotes. Chitin and/or chitosan MPs (< 40 μm) were subcutaneously injected in the BALB/c mice with two-day intervals until two weeks. Mice in all groups were sacrificed at 12 weeks post-infection. Enumeration of viable parasites was performed using limiting dilution assay. Furthermore, the animals (5 mice/group) were sacrificed two weeks post-infection. The lymph node cells were isolated and the effects of the chitinous MPs on the proliferation and production of cytokines such as tumor necrosis factor alpha (TNF-α) and interleukin-10 (IL-10) were determined. The mean sizes of lesions were significantly smaller in chitin (0.6 ± 0.12 mm) and chitosan treated groups (1.2 ± 0.8 mm) than in the control group (6.2 ± 1.7 mm) (P < 0.05). The parasite load in the lymph nodes of the treated mice was significantly lower than that in the lymph nodes of controls (1.31 × 10⁶ vs 8.24 × 10⁷ parasite/lymph node [P = 0.032] and 7.49 × 10⁶ vs 8.24 × 10⁷ parasite/lymph node [P = 0.05] for chitin and chitosan MPs treatment, respectively). We found that chitinous MPs induced cell proliferation and that chitin but not chitosan increased TNF-α and IL-10 production. Chitin appears that it has more effect than chitosan against leishmaniasis. The current study revealed that chitinous MPs had significant activity against L. major and could be considered as new therapeutic modality in leishmaniasis.     

Apolipoprotein A-I inhibits chemotaxis,adhesion, activation of THP-1 cells and improves the plasma HDL inflammatory index

The anti-inflammatory effects of high density lipoprotein (HDL) are well described, however, such effects of Apolipoprotein A-I (ApoA-I) are less studied. Building on our previous study, we further explored the mechanism of anti-inflammatory effects of ApoA-I, and focused especially on the interaction between monocyte and endothelial cells and plasma HDL inflammatory index in LPS-challenged rabbits. Our results show that ApoA-I significantly decreased LPS-induced MCP-1 release from THP-1 cells and ox-LDL-induced THP-1 migration ratio (P < 0.01, respectively). ApoA-I significantly decreased sL-selectin, sICAM-1 and sVCAM-1 release (P < 0.01, P < 0.01, P < 0.05, respectively) from LPS-stimulated THP-1 cells. Furthermore, ApoA-I significantly inhibited LPS-induced CD11b and VCAM-1 expression on THP-1 cells (P < 0.01, P < 0.05, respectively). ApoA-I diminished LPS-induced mCD14 expression (P < 0.01) and NFκB nuclear translocation in THP-1 cells. After single dose treatment of ApoA-I, the value of plasma HDL inflammatory index in LPS-challenged rabbits was improved significantly (P < 0.05). These results suggest that ApoA-I can inhibit chemotaxis, adhesion and activation of human monocytes and improve plasma HDL inflammatory index with presenting beneficial anti-inflammatory effects.