Influence of hormone replacement therapy and aspirin on temperature regulation in postmenopausal women

Postmenopausal women receiving estrogen-replacement therapy (ERT) regulate body temperature (T(b)) at a lower level than women not receiving hormone replacement therapy (untreated) and women using estrogen plus progesterone therapy (E + P), but it is not clear if reproductive hormones alter T(b) by directly acting on central thermoregulatory centers or indirectly via a secondary mediator(s). The purpose of the present investigation was to examine the possible involvement of pyrogenic cytokines and cyclooxygenase (COX) products (e.g., prostaglandins) in the regulation of T(b) in three groups of postmenopausal women (8 ERT, 7 E + P, and 8 untreated). We measured ex vivo secretion of cytokine agonists [tumor necrosis factor (TNF)-alpha and interleukin (IL)-1beta and -6] and modifiers (IL-2 soluble receptor, IL-1 receptor antagonist, soluble TNF receptor type I, soluble TNF receptor type II, soluble IL-6 receptor, and soluble glycoprotein 130) from peripheral blood mononuclear cells and thermoregulatory responses at rest and during 1 h of passive whole body heating in the postmenopausal women before and after 3 days of placebo or aspirin (50 mg. day(-1). kg(-1)). With and without aspirin, the ERT group had a lower baseline rectal temperature (T(re); 0.44 degrees C, P < 0.004) and a reduced T(b) threshold for cutaneous vasodilation (0.29 degrees C and 0.38 degrees C, P < 0.01) compared with the untreated and E + P groups, respectively. In the placebo condition, waking morning oral temperature (T(or)) correlated with ex vivo secretion of the proteins associated with IL-6 bioactivity. Aspirin caused significant reductions in waking T(or) in the E + P group and in baseline T(re) in the untreated group. However, the difference in thermoregulation brought about by steroid hormone treatment could not be explained by these relatively modest apparent influences by cytokines and COX products. Therefore, the altered thermoregulation induced by reproductive steroid therapy appears to occur via a mechanism distinct from a classic infection-induced fever.     

Toll-like receptor 4 and CD14 mRNA expression are lower in resistive exercise-trained elderly women.

The purpose of this study was to examine the influence of resistive exercise training and hormone status on mRNA expression of toll-like receptor 4 (TLR4), CD14, IL-1beta, IL-6, and TNF-alpha. Resistive exercise-trained women on "traditional" hormone replacements [hormone replacement therapy (HRT), n = 9], not taking hormones (NHR, n = 6), or taking medications known to influence bone (MIB, n = 7) were compared with untrained subjects not taking supplemental hormones (Con, n = 6). Blood was taken from trained subjects before, immediately after, and 2 h after resistive exercise (same time points for resting Con). TLR4 mRNA expression (RT-PCR) was not different among groups or across time but was significantly (P = 0.044) lower (1.9-fold) when trained groups were collapsed and compared with Con. There was also a significant group effect (P < 0.0001) for TLR4 mRNA when expressed per monocyte. CD14 expression was significantly (P = 0.006) lower (2.3-fold) for training groups collapsed and compared with Con. CD14 mRNA, expressed per monocyte, was significantly lower immediately after resistive exercise for NHR, HRT, and MIB compared with Con. There were few significant effects detected for IL-6, IL-1beta, and TNF-alpha mRNA, but there was a significant group effect (P < 0.0001) for TNF-alpha mRNA expressed per monocyte (Con > HRT, NHR, MIB). These findings suggest that there may be a resistive exercise training-induced reduction in TLR4/CD14 expression in older women. Further research is needed to determine whether lower TLR4/CD14 could explain the lower LPS-stimulated inflammatory cytokines observed in these women.     

Effect of postmenopausal hormone replacement therapy on lipoprotein and homocysteine levels in Chinese women.

Epidemiological studies have revealed that postmenopausal estrogen replacement therapy results in a marked reduction in the risk for cardiovascular diseases. In the present study, we evaluated plasma lipoprotein profile as well as homocysteine levels in 145 postmenopausal and premenopausal Chinese women living in Hong Kong. We also investigated the effect of hormone-replacement therapy (HRT) with estrogen or estrogen combined with progestin on plasma lipoprotein profile and homocysteine concentrations in those individuals. Postmenopausal women displayed significantly higher plasma levels of total cholesterol, LDL-cholesterol and apoB as well as higher plasma homocysteine levels than that of premenopausal women. HRT with either estrogen (17beta-estradiol or conjugated equine estrogen) alone or estrogen combined with progestin for 3.5-4.5 years significantly improved the lipoprotein profile in postmenopausal women by decreasing the levels of total cholesterol (12-20% reduction), LDL-cholesterol (26-29% reduction) and apoB (21-25% reduction). In women treated with 17beta-estradiol or conjugated equine estrogens their plasma levels of apoAl were significantly elevated (18% elevation) as compared to non-users. HRT also reduced plasma concentrations of homocysteine (13-15% reduction). In conclusion, we found that long-term HRT was associated with improvement in plasma lipoprotein profile and a reduction in homocysteine concentration in postmenopausal women. These results support the notion that the improvement of lipoprotein profile and a reduction in homocysteine concentration may contribute to the beneficial effect of HRT on cardiovascular risk.     

Prevalence of estrogen receptor alpha PvuII and XbaI polymorphism in population of Polish postmenopausal women

Numerous data indicate that polymorphism of estrogen receptor alpha (ERalpha) may predict lipid levels, lipid response to hormone replacement therapy (HRT), myocardial infarction risk, bone fracture risk, bone mineral density (BMD) and changes in BMD over time. In this study we aimed to evaluate distribution of ERalpha PvuII and XbaI genotypes in population of Polish postmenopausal women qualified to different protocols of HRT. Subject of the study were 64 consecutive postmenopausal women aged from 45 to 65 years (mean 56.6) assigned to HRT. ERalpha PvuII and XbaI polymorphism was determined by PCR-restriction fragment length polymorphism (RFLP). The absence of PvuII and XbaI restriction sites were indicated by "P" and "X" and presence by "p" and "x", respectively. PvuII genotype was distributed as follows: PP 17.2% (n=11), Pp 50% (n=32), pp 32.83% (n=21). Frequency of XbaI genotype was: XX 6.25% (n=4), Xx 34.4% (n=22), xx 59.4% (n=38). Four haplotypes with following frequencies were recognized: PX 17.3%, px 47.4%, Px 24.4% and pX 10.9%. Prevalence of estrogen receptor alpha PvuII and XbaI polymorphisms in Polish women is similar to previously studied population.     

Progesterone, but not 17beta-estradiol, increases TNF-alpha secretion in U937 monocytes

The Women Health Initiative Clinical trial results suggest that post-menopausal women receiving estrogen + progesterone are at risk for heart disease compared with estrogen alone supplemented women. We examined the hypothesis that progesterone but not 17beta-estradiol (E) increases the secretion of pro-inflammatory cytokines interleukin (IL)-6 and tumor necrosis factor (TNF)-alpha. U937 human monocytes were cultured with normal or high glucose in the presence and absence of estrogen or progesterone at 37 degrees C for 24 h. Results show that estrogen inhibits IL-6 but not TNF-alpha secretion (p < 0.05) in monocytes activated by lipopolysaccharide (LPS) or high glucose. In addition, progesterone increased the TNF-alpha secretion in activated monocytes. Thus, progesterone supplementation along with estrogen may increase blood levels of pro-inflammatory cytokine TNF-alpha and thus risk of heart disease in post-menopausal women.     

Effect of chromium niacinate and chromium picolinate supplementation on lipid peroxidation, TNF-alpha, IL-6, CRP, glycated hemoglobin, triglycerides, and cholesterol levels in blood of streptozotocin-treated diabetic rats

Chromium (Cr(3+)) supplementation facilitates normal protein, fat, and carbohydrate metabolism, and is widely used by the public in many countries. This study examined the effect of chromium niacinate (Cr-N) or chromium picolinate (Cr-P) supplementation on lipid peroxidation (LP), TNF-alpha, IL-6, C-reactive protein (CRP), glycosylated hemoglobin (HbA(1)), cholesterol, and triglycerides (TG) in diabetic rats. Diabetes (D) was induced in Sprague-Dawley rats by streptozotocin (STZ) (ip, 65 mg/kg BW). Control buffer, Cr-N, or Cr-P (400 microg Cr/kg BW) was administered by gavages daily for 7 weeks. Blood was collected by heart puncture using light anesthesia. Diabetes caused a significant increase in blood levels of TNF-alpha, IL-6, glucose, HbA(1), cholesterol, TG, and LP. Compared with D, Cr-N supplementation lowered the blood levels of TNF-alpha (P=0.04), IL-6 (P=0.02), CRP (P=0.02), LP (P=0.01), HbA(1) (P=0.02), TG (P=0.04), and cholesterol (P=0.04). Compared with D, Cr-P supplementation showed a decrease in TNF-alpha (P=0.02), IL-6 (P=0.02), and LP (P=0.01). Chromium niacinate lowers blood levels of proinflammatory cytokines (TNF-alpha, IL-6, CRP), oxidative stress, and lipids levels in diabetic rats, and appears to be a more effective form of Cr(3+) supplementation. This study suggests that Cr(3+) supplementation can lower the risk of vascular inflammation in diabetes.     

Plasma C-reactive protein is not elevated in physically active postmenopausal women taking hormone replacement therapy.

We tested the hypothesis that hormone replacement therapy (HRT)-related increases in C-reactive protein (CRP) would either be blunted or absent in postmenopausal women who regularly perform endurance exercise. Plasma CRP is an independent predictor of future cardiovascular events in healthy men and women. Oral HRT increases plasma CRP concentrations in postmenopausal women. Regular aerobic exercise reduces the risk of cardiovascular events and is associated with lower CRP concentrations in adults. To date, no study has evaluated the influence of habitual physical activity on the elevation of CRP associated with HRT. Plasma CRP concentrations were measured in 114 postmenopausal women: 39 physically active (endurance trained) and 75 sedentary postmenopausal subjects. Sixty-five women were users of HRT (22 physically active and 43 sedentary), and 49 were nonusers (17 physically active and 32 sedentary). CRP levels were approximately 75% higher (P < 0.01) in the sedentary users vs. nonusers of HRT (1.9 +/- 1.8 vs. 1.1 +/- 1.0 mg/l). In contrast, there was no difference in CRP levels between the physically active users and nonusers of HRT (0.6 +/- 0.4 vs. 0.4 +/- 0.2 mg/l; P = 0.61). Regardless of HRT status, CRP concentrations were approximately 65% lower in the physically active compared with sedentary women. In conclusion, physically active postmenopausal women exhibit lower plasma CRP concentrations compared with sedentary controls. Importantly, the HRT-related elevation in plasma CRP levels observed in sedentary women is absent in women who engage in regular endurance exercise. These data suggest that habitual physical activity may prevent the elevation in CRP concentrations due to HRT.     

Variability of serum levels of tumor necrosis factor-alpha, interleukin 6, and soluble interleukin 6 receptor over 2 years in young women

Serum levels of tumor necrosis factor-alpha (TNF-alpha), interleukin 6 (IL-6), and soluble interleukin 6 receptor (sIL-6R) have been studied as risk factors of cardiovascular disease in longitudinal studies. However, it is unknown about their long-term intra-individual variations and whether single measurements of these cytokines and receptor are reliable biomarkers in epidemiological studies. In this study, serum levels of TNF-alpha, IL-6, and sIL-6R were assayed by ELISAs in 36 young, healthy women from whom three blood samples were collected at 12-month intervals over 2 years, and the intraclass correlation coefficients (ICC) were estimated. The ICC of 0.73 (95% CI=0.49-0.79) for TNF-alpha was comparable to those of other commonly used biomarkers, justifying its use in epidemiological studies. The ICC of 0.48 (95% CI=0.25-0.58) for IL-6 was not optimal. However, IL-6 has been demonstrated as a consistent risk factor for cardiovascular disease, suggesting it could still be a useful biomarker if its disease association is substantial. The ICC of 0.36 (95% CI=0.10-0.47) for sIL-6R was relatively low, and multiple samples would need to be collected in prospective studies for this receptor.     

Effect of hormone replacement therapy on the production of bone-resorbing cytokines by peripheral blood cells in postmenopausal women.

We studied the effects of hormone replacement therapy (HRT) with estrogen on postmenopausal changes in the production of bone-resorbing cytokines interleukin 1 beta (IL-1beta) and tumor necrosis factor alpha (TNFalpha). Both cytokines were measured in the supernatants of lipopolysaccharide (LPS)-stimulated whole-blood cells from 72 untreated and 44 HRT-treated women by ELISA. The levels of IL-1beta were significantly higher in women in their 40s and 50s and in postmenopausal women than in women in their teens, 20s and 30s, while the levels of TNFalpha did not show any changes related to age. Both levels in HRT-treated women were significantly lower than those in untreated women at almost every postmenopausal stage. In a prospective study, HRT induced significant declines in both levels. These results show that estrogen decreases the accelerated production of IL-1beta and reduces the production of TNFalpha in postmenopausal women at each postmenopausal stage, even in late-postmenopausal women.     

Hormone replacement therapy in rheumatoid arthritis is associated with lower serum levels of soluble IL-6 receptor and higher insulin-like growth factor 1

Hormone replacement therapy (HRT) modulates the imbalance in bone remodeling, thereby decreasing bone loss. Sex hormones are known to influence rheumatic diseases. The aim of this study was to investigate the effects of HRT on the serum levels of hormones and cytokines regulating bone turnover in 88 postmenopausal women with active rheumatoid arthritis (RA) randomly allocated to receive HRT plus calcium and vitamin D3 or calcium and vitamin D3 alone for 2 years. An increase in estradiol (E2) correlated strongly with improvement of bone mineral density in the hip (P < 0.001) and lumbar spine (P < 0.001). Both baseline levels and changes during the study of IL-6 and erythrocyte sedimentation rate were correlated positively (P < 0.001). HRT for 2 years resulted in an increase of the bone anabolic factor, insulin-like growth factor 1 (IGF-1) (P < 0.05) and a decrease of serum levels of soluble IL-6 receptor (sIL-6R) (P < 0.05), which is known to enhance the biological activity of IL-6, an osteoclast-stimulating and proinflammatory cytokine. Baseline levels of IL-6 and IGF-1 were inversely associated (P < 0.05), and elevation of IGF-1 was connected with decrease in erythrocyte sedimentation rate (P < 0.05) after 2 years. Interestingly, increase in serum levels of E2 was associated with reduction of sIL-6R (P < 0.05) and reduction of sIL-6R was correlated with improved bone mineral density in the lumbar spine (P < 0.05). The latter association was however not significant after adjusting for the effect of E2 (P = 0.075). The influences of IGF-1 and the IL-6/sIL-6R pathways suggest possible mechanisms whereby HRT may exert beneficial effects in RA. However, to confirm this hypothesis future and larger studies are needed.     

Increased systemic and adipose tissue cytokines in patients with HIV-associated lipodystrophy

The lipodystrophy syndrome (adipose tissue redistribution and metabolic abnormalities) observed with highly active antiretroviral therapy (HAART) during human immunodeficiency virus (HIV) infection may be related to increased proinflammatory cytokine activity. We measured acute cytokine (TNF-alpha, IL-6, leptin), glycerol, and lactate secretion from abdominal subcutaneous adipose tissue (SAT), and systemic cytokine levels, in HIV-infected subjects with and without lipodystrophy (HIVL+ and HIVL-, respectively) and healthy non-HIV controls. Lipodystrophy was confirmed and characterized as adipose tissue redistribution in HIVL+ compared with HIVL- and controls, by dual-energy X-ray absorptiometry and by whole body MRI. TNF-alpha secretion from abdominal SAT and circulating levels of IL-6, soluble TNF receptors I and II, and insulin were elevated in HIVL+ relative to HIVL- and/or controls, particularly in HIVL+ undergoing HAART. In the HIV-infected group as a whole, IL-6 secretion from abdominal SAT and serum IL-6 were positively associated with visceral fat and were negatively associated with the relative amount of lower limb adipose tissue (P < 0.01). Decreased leptin and increased lactate secretion from abdominal SAT were specifically associated with HAART. In conclusion, increased cytokine secretion from adipose tissue and increased systemic proinflammatory cytokine activity may play a significant role in the adipose tissue remodeling and/or the metabolic abnormalities associated with the HIV-lipodystrophy syndrome in patients undergoing HAART.     

Relations between IL-3-induced proliferation and in vitro cytokine secretion of bone marrow cells from AML patients.

The influence of IL-3 on the bone marrow cells of 53 patients with acute myeloid leukaemia (AML) was investigated after 72 h suspension in cultures by analysing the proliferation of blasts and the secretion of cytokines. The titres of IL-1beta IL-6, TNF-alpha and IL-3 were measured in the supernatants of these cultures with ELISA tests. Comparing the percentage of cells in S-phases of control cultures and cultures with IL-3, the leukaemias were divided into two growth pattern groups: IL-3-insensitive (n=19) and IL-3-sensitive (n=34) leukaemias. The IL-3-insensitive AML cells show a greater ability for autonomous growth, first by the increase of S-phase in the control culture compared with the S-phase in vivo (P=0.0486) and second, by the higher constitutive secretion (control culture) of IL-1beta P =0.0004), IL-6 ( P =0.0395) and TNF-alpha P=0.0005). The IL-3-induced secondary cytokine secretion is also different in the two growth pattern groups. Whereas in the IL-3-insensitive AML cells a moderate increase of IL-1beta (1.48-fold increase) was present, in the IL-3-sensitive AML cells a 4.72-fold increase of IL-1beta 2.71-fold increase of IL-6 and 11.81-fold increase of the TNF-alpha titre could be detected. Overall, the data show an inverse correlation between the ability of AML cells to respond to IL-3 with increase of an S-phase and the constitutive secretion of IL-1beta, II-6 and TNF-alpha. A further effect of IL-3 is the induction of secondary cytokine secretion in the bone marrow of IL-3-sensitive growing AML cells.     

Evaluation of tumour necrosis factor alpha, interleukin-2 soluble receptor, nitric oxide metabolites, and lipids as inflammatory markers in type 2 diabetes mellitus

This study compared the results of tumour necrosis factor alpha (TNF-alpha), interleukin-2 soluble receptor (sIL-2R), nitric oxide metabolites (NO(x)), C-reactive protein (CRP), and lipids (total cholesterol, high-density lipoprotein (HDL-cholesterol), low-density lipoprotein (LDL-cholesterol), and triglycerides) between control group (nondiabetic subjects) and overweight type 2 DM subjects. To restrict the influence of variables that could interfere in the interpretation of data, subjects with obesity and/or acute or chronic inflammatory disease, haemoglobinopathies, recent use of antibiotics, antiinflammatory drugs, and trauma were excluded. Type 2 DM patients (n = 39; age 53.3 +/- 9.0 years; median glycated haemoglobin A(1c)< 8%) presented higher levels of TNF-alpha, triglycerides (P < .01), NO(x) and sIL-2R (P < .05) than control group (n = 28; age 39.7 +/- 14.1 years). CRP, LDL-cholesterol, total cholesterol, and HDL-cholesterol did not differ among groups. Diabetic women (n = 21) had higher levels of TNF-alpha, total cholesterol, LDL-cholesterol, and HDL-cholesterol than diabetic men (n = 18) (P < .05), but there were no differences among sexes in the control group. This study indicates that increased level of proinflammatory markers occurs in type 2 DM even in the absence of obesity and marked hyperglycaemia, confirming that the inflammation course of the atherosclerotic process is more severe in diabetic patients than in nondiabetic subjects.     

Antiestrogenic activities of Ginkgo biloba extracts

Most climacteric and postmenopausal women appear to have vasomotor symptoms as well as a high risk of osteoporosis and cardiovascular disease. Although exogenous estrogens can reduce these symptoms, women are reluctant to use hormone replacement therapy (HRT) due to its undesirable side effects, such as irregular bleeding and an increased risk of breast cancer. A previous study suggested that Ginkgo biloba extracts (GBE) have estrogenic activity and might be suitable as an alternative to HRT. However, there are no reports of the preventive effect of GBE on breast cancer, which is the side effect of classical HRT. In this study, it was confirmed that GBE exhibits estrogenic and antiestrogenic activity depending on the E₂ and GBE concentration, via estrogen receptor (ER)-dependent and ER-independent pathways. In addition, GBE reduced the E₂ levels by stimulating the E₂ metabolism and inhibiting E₂ synthesis, which indicates that GBE can induce antiestrogenic activity via the depletion of E₂. Furthermore, GBE might have similar action to selective arylhydrocarbon receptor modulators (SAhRMs), which induce antiestrogenic activity through cross-talk between the arylhydrocarbon receptor (AhR) and ER. In conclusion, GBE has a biphasic effect on estrogen, and can be considered as a potential alternative to HRT with chemopreventive effects on breast cancer. However, further studies on animals and humans will be required.     

Flow cytometrical determination of interleukin 1beta, interleukin 6 and tumour necrosis factor alpha in monocytes of rheumatoid arthritis patients; relation with parameters of osteoporosis.

Experimental data suggest that pro-inflammatory cytokines such as interleukin 1beta (IL-1beta), interleukin 6 (IL-6) and tumour necrosis factor alpha (TNF-alpha) are important in the pathogenesis of osteoporosis in rheumatoid arthritis. Therefore we compared the production of these cytokines by monocytes in 10 rheumatoid arthritis patients and 10 controls. Cytokine levels in rheumatoid arthritis patients were related to disease activity parameters, bone mineral density (BMD) corrected for age and sex (Z scores) and osteocalcin as a laboratory parameter of bone remodelling. Cytokines were determined by a flow cytometrical technique. There was a tendency for higher IL-1beta levels in patients compared with controls. A positive correlation between erythrocyte sedimentation rate and spontaneous production of monocytic cytokines was found. Z scores of the lumbar spine showed a negative correlation with spontaneous production of IL-1beta and IL-6. Plasma osteocalcin levels were positively correlated with spontaneous production of IL-1beta, IL-6 and TNF-alpha. In conclusion, the correlation of the levels of these cytokines with parameters of bone metabolism and osteoporosis suggest that especially IL-1beta and IL-6 are associated with more pronounced osteoporosis in active rheumatoid arthritis.     

Effect of postmenopausal hormone replacement therapy on lipoprotein and homocysteine levels in Chinese women

Epidemiological studies have revealed that postmenopausal estrogen replacement therapy results in a marked reduction in the risk for cardiovascular diseases. In the present study, we evaluated plasma lipoprotein profile as well as homocysteine levels in 145 postmenopausal and premenopausal Chinese women living in Hong Kong. We also investigated the effect of hormonereplacement therapy (HRT) with estrogen or estrogen combined with progestin on plasma lipoprotein profile and homocysteine concentrations in those individuals. Postmenopausal women displayed significantly higher plasma levels of total cholesterol, LDLcholesterol and apoB as well as higher plasma homocysteine levels than that of premenopausal women. HRT with either estrogen (17-estradiol or conjugated equine estrogen) alone or estrogen combined with progestin for 3.5–4.5 years significantly improved the lipoprotein profile in postmenopausal women by decreasing the levels of total cholesterol (12–20% reduction), LDL-cholesterol (26–29% reduction) and apoB (21–25% reduction). In women treated with 17estradiol or conjugated equine estrogens their plasma levels of apoAI were significantly elevated (18% elevation) as compared to non-users. HRT also reduced plasma concentrations of homocysteine (13–15% reduction). In conclusion, we found that long-term HRT was associated with improvement in plasma lipoprotein profile and a reduction in homocysteine concentration in postmenopausal women. These results support the notion that the improvement of lipoprotein profile and a reduction in homocysteine concentration may contribute to the beneficial effect of HRT on cardiovascular risk.     

Serum proinflammatory mediators at different periods of therapy in patients with multiple myeloma

Multiple myeloma (MM) is a malignant disease characterized by the clonal proliferation of plasma cells within the bone marrow. Several cytokines have been demonstrated to be involved in the control of growth, progression, and dissemination of MM. We determined serum levels of interleukin-1beta (IL-1beta), soluble interleukin-2 receptor (sIL-2R), interleukin-6 (IL-6), interleukin-8 (IL-8), tumor necrosis factor-alpha (TNF-alpha), and C-reactive protein (CRP) in 14 newly diagnosed MM patients. The median age of the patients was 63.4 +/- 10.8 years and all of the patients were stage III (classified according to the Durie-Salmon classification). The same parameters were measured in 15 healthy controls. In addition, we also examined the effects of vincristine-adriamycin-dexamethasone (VAD) therapy on the same parameters and mediators as well as the relationship among the parameters in the same patient groups. The serum concentrations of TNF-alpha, IL-1beta, sIL-2R, IL-6, IL-8, and CRP (18.6 +/- 3.7 pg/mL, 10.1 +/- 2.8 pg/mL, 730 +/- 220 U/mL, 11.4 +/- 3.3 pg/mL, 23.9 +/- 8.3 pg/mL, and 49.9 +/- 19.5 mg/dL, resp) were significantly higher in newly diagnosed MM patients than in healthy controls (P < .0001). All of the parameters were found to be significantly reduced after chemotherapy. In conclusion, we found that after the VAD therapy, the level of these cytokines which are thought to play an important role in the pathogenesis of MM was significantly suppressed. This is the first study demonstrating strong impact of VAD treatment on circulating mediators of sIL-2R and IL-8 levels parameters.     

Postoperative changes in serum cytokines profile and nitric oxide levels in patients with cystic echinococcosis

The aim of the present study was to examine serum cytokines and nitric oxide (NO) levels in patients with cystic echinococcosis (CE). 28 patients with CE were studied and all underwent surgery. Serum levels of tumour necrosis factor-alpha (TNF-alpha), interleukin IL-1beta, receptor of soluble IL-2R (sIL-2R), IL-6, IL-8, nitrate/nitrite, and C-reactive protein (CRP) were determined before and after induction of treatment. Data were compared with those obtained from 28 healthy volunteers. IL-6 was elevated in all CE patients (100%). IL-8 was increased in 11/28 (39.3%). Increased levels of IL-2R and TNF-alpha were found in a limited number of them particularly those showing cysts in the central area of the liver (5/28, 6/28). IL-1beta level was not elevated in any patient except in secondary severe CE. CRP and nitrate/nitrite levels were also increased. A positive correlation between CRP and IL-6 (r = 0.74; p < 0.001) was found confirming the link between inflammation due to CE and activation of monocytes. All patients completely recovered and the levels of the studied parameters reverted to normal levels except one patient in whom severe recurrent disease occurred two years after the first operation. These results suggest that there are different immunoregulatory events and cytokines response during CE and may be in part related to slight monocytosis and in part to Th2 activation. IL-6, NO and CRP were unambiguously involved in the host parasite interaction and therefore may be useful markers in monitoring CE management and evaluating surgical stress.     

Impact of long-term hormone replacement therapy on in vivo and in vitro markers of lipid oxidation

Postmenopausal hormone replacement therapy (HRT) with estrogen has been suggested to inhibit oxidation of low-density lipoprotein (LDL) in vitro, but progestins may oppose this effect. We studied whether estrogen HRT and combined HRT with estrogen and progestin differ in their ability to resist in vivo and in vitro oxidation of lipids. Study group included 15 women on oestradiol valerate (mean age 56 years, treatment duration 10.5 years) and 15 women on combined HRT with oestradiol valerate and levonorgestrel (mean age 58 years, treatment duration 11.3 years). In addition to lipid and apolipoprotein concentrations, the lagtime of LDL to oxidation, the rate of the propagation phase and the maximum concentration of conjugated dienes were recorded as indices of LDL susceptibility to copper-induced oxidation in vitro. As an in vivo marker of oxidative stress we measured 24-h excretion of urinary 8-iso-prostaglandin F2alpha (8-iso-PGF2alpha). All measurements were done after long-term HRT (baseline), after 4 weeks pause and again 3 weeks after reintroduction of HRT. High-density lipoprotein (HDL) cholesterol and apolipoprotein AI concentrations were significantly higher and LDL to HDL ratio significantly lower after long-term oestradiol valerate therapy than after combined therapy. Simultaneously, the triglyceride and lipoprotein (a) levels were higher in the estrogen group. Susceptibility of LDL to oxidation and the level of 8-iso-PGF2alpha were similar in both groups at all measurement points, and treatment group was not a statistically significant determinant of these markers at baseline. According to these results, estrogen and combined HRT do not differ in their abilities to oppose LDL oxidation in vitro or systemic oxidative stress in vivo, but have differential effects on blood lipids.