Plasma and scales levels of interleukin 18 in comparison with other possible clinical and laboratory biomarkers of psoriasis activity

The aim of the study was to assess plasma and scales levels of interleukin (IL) 18 collected from psoriatic patients with different disease activity. IL-18 concentrations were measured using an enzyme immunoassay in the plasma and scales of 34 patients with chronic plaque type psoriasis. IL-18 levels were analysed with respect to plasma-transforming growth factor β₁ (TGF-β₁), the disease duration and the duration of the present relapse, and psoriasis area and severity index (PASI). Plasma IL-18 concentration varied from 90 to 1300 pg ml^-1 and means (368.2±42.4 pg ml^-1) were significantly elevated in comparison with healthy controls (205.9±31.8 pg ml^-1). The presence of IL-18 was also demonstrated in scales from skin lesions. Treatment caused a significant decrease of plasma IL-18 concentration to 250.2±13.8 pg ml^-1. There was a significant correlation between plasma IL-18 levels and PASI values (r=0.554). There was no correlation between IL-18 concentration in scales and PASI, between IL-18 concentrations in plasma and scales, and between plasma IL-18 and the disease duration or duration of present relapse. Plasma TGF-β₁ concentration demonstrated a significant correlation with PASI (r=0.353), but not with IL-18 levels in plasma (r=0.063) and scales (0.141). The sum of plasma levels of IL-18 and TGF-β₁ divided by the optimal coefficient demonstrated a statistically significant correlation with the highest r-value. The findings confirm an association between plasma IL-18 concentration and psoriasis severity. Moreover, it was shown that combined measurement of IL-18 and TGF-β₁ in plasma can be considered as a possible biomarker of psoriasis activity.     

Effect of ulcerative colitis treatment on transforming growth factor beta(1) in plasma and rectal mucosa

The aim of this study was to evaluate the effect of active ulcerative colitis (UC) treatment on transforming growth factor beta(1) (TGF-beta(1)) concentration in plasma and rectal mucosa measured in 28 patients. The highest plasma values were observed in patients with the severe course of the disease (74.2+/-14.0 ng/ml), and they were significantly higher than in the group with mild one (43.7+/-5.6 ng/ml). Mean TGF-beta(1) measured in mucosal samples from patients with severe UC (563+/-146 pg/mg protein) doubled values from patients with mild UC (286+/-65 pg/mg protein). Plasma and mucosal TGF-beta(1) correlated significantly with disease activity index (DAI) and clinical activity index (CAI). Plasma TGF-beta(1) correlated additionally with scored endoscopic degree of mucosal injury. Treatment caused significant decrease of plasma and mucosal TGF-beta(1) concentrations. Patients who responded completely had higher baseline plasma and mucosal TGF-beta(1) that decreased significantly after the treatment. These results show that plasma and mucosal concentrations of transforming growth factor beta(1) are strongly associated with ulcerative colitis activity, and successful treatment of the disease results with decrease of their levels. More effective response to the treatment can be achieved in patients with higher baseline concentrations of TGF-beta(1).     

Plasma transforming growth factor beta1 as a biomarker of psoriasis activity and treatment efficacy.

Transforming growth factor-beta(1) (TGFbeta(1)) is thought to be an inhibitor of the keratinocyte hyperproliferation associated with psoriasis. The aim of this study was to evaluate plasma TGFbeta(1) and TGFbeta(2) concentrations in psoriatic patients as possible indicators of treatment efficacy. TGFbeta concentrations were measured in the plasma of 26 patients with psoriasis using an enzyme immunoassay and analysed with respect to the psoriasis area and severity index (PASI) before and after treatment with salicylic acid and/or sulphur followed by dithranol ointment. Baseline plasma concentrations of both TGFbeta(1) and TGFbeta(2) (20.3+/-2.2 ng ml(-1) and 0.14+/-0.02 ng ml(-1), respectively) did not differ significantly from control values (18.3+/-1.6 ng ml(-1) and 0.14+/-0.03 ng ml(-1), respectively). However, a significant positive correlation (r=0.69) between the baseline PASI and TGFbeta(1), but not TGFbeta(2), values was demonstrated. The pretreatment TGFbeta(1) concentration in patients with a PASI >/=15 (26.6+/-3.2 ng ml(-1)) was significantly higher than control values. There were no significant elevation of pretreatment TGFbeta(1) concentrations in patients with a PASI<15, or with respect to TGFbeta(2) in both groups. Treatment caused a significant decrease in TGFbeta(1), but only in patients with a PASI>/=15. Patients with baseline TGFbeta(1) concentrations exceeding the mean of the control group had a PASI value that was significantly higher than that of patients with a TGFbeta(1) concentration below the mean of the controls. These results confirmed an association between plasma TGFbeta(1) concentration and psoriasis severity, and demonstrated its normalization during treatment. Measurement of TGFbeta(1) in plasma should be considered as a possible biomarker of psoriasis activity during its management.     

Plasma and scales levels of interleukin 18 in comparison with other possible clinical and laboratory biomarkers of psoriasis activity

Abstract

The aim of the study was to assess plasma and scales levels of interleukin (IL) 18 collected from psoriatic patients with different disease activity. IL-18 concentrations were measured using an enzyme immunoassay in the plasma and scales of 34 patients with chronic plaque type psoriasis. IL-18 levels were analysed with respect to plasma-transforming growth factor β₁ (TGF-β₁), the disease duration and the duration of the present relapse, and psoriasis area and severity index (PASI). Plasma IL-18 concentration varied from 90 to 1300 pg ml^?1 and means (368.2±42.4 pg ml^?1) were significantly elevated in comparison with healthy controls (205.9±31.8 pg ml^?1). The presence of IL-18 was also demonstrated in scales from skin lesions. Treatment caused a significant decrease of plasma IL-18 concentration to 250.2±13.8 pg ml^?1. There was a significant correlation between plasma IL-18 levels and PASI values (r=0.554). There was no correlation between IL-18 concentration in scales and PASI, between IL-18 concentrations in plasma and scales, and between plasma IL-18 and the disease duration or duration of present relapse. Plasma TGF-β₁ concentration demonstrated a significant correlation with PASI (r=0.353), but not with IL-18 levels in plasma (r=0.063) and scales (0.141). The sum of plasma levels of IL-18 and TGF-β₁ divided by the optimal coefficient demonstrated a statistically significant correlation with the highest r-value. The findings confirm an association between plasma IL-18 concentration and psoriasis severity. Moreover, it was shown that combined measurement of IL-18 and TGF-β₁ in plasma can be considered as a possible biomarker of psoriasis activity.     

Selenium status in psoriasis and its relationship with alcohol consumption

The aim of the study was to examine the influence of alcohol consumption on the severity of psoriasis and selenium (Se) concentration and Se-dependent gluathione peroxidase activity in plasma (pl-GSH-Px) and in erythrocytes (RBC-GSH-Px) in psoriatic patients. Thirty-five in-patients with psoriasis lasting <10 mo and 42 with psoriasis lasting >3 yr constituted groups 1 and 2, respectively. The severity of psoriasis was assessed using the PASI scoring system and the consumption of alcohol, using a structured questionnaire. The Se concentration was 47.11±11.61 μg/L in group 1 and 38.69±13.22 μg/L in group 2 (p<0.05), the pl-GSH-Px was 0.15±0.04 U/mL and 0.14±0.04 U/mL (p>0.05), and the RBC-GSH-Px was 13.97±4.27 U/g Hb and 13.16±3.85 U/g Hb (p>0.05), respectively. In excessive drinkers (<10% of patients, all males), the Se concentration was 32.84±10.88 μg/L, the pl-GSH-Px was 0.15±0.03 U/mL, and the RBC-GSH-Px was 11.64±3.32 U/g Hb. A low RBC-GSH-Px correlated to the consumption of high-grade alcoholic beverages (R=−0.45, p<0.05) and to the PASI value (R=−0.37, p<0.05) in group 2. Depressed Se concentration and Se-dependent GSH-Px can be related to the severity and a duration of psoriasis. The excessive consumption of alcohol is associated with severity of the disease and with low activity of GSH-Px in erythrocytes in patients with long-lasting psoriasis.     

Plasma levels of interleukin-12 (IL-12), interleukin-18 (IL-18) and transforming growth factor beta (TGF-beta) in Plasmodium falciparum malaria

The interaction between pro- and anti-inflammatory cytokines such as interleukin 12 (IL-12), interleukin 18 (IL-18) and transforming growth factor beta (TGF-beta) may play an important role in malaria pathogenesis and outcome. IL-18 cooperates with IL-12 in the IFN-gamma production by T, B, and NK cells, and synergizes with IL-12 for IFN-gamma production by Th1 cells. Recently it has been demonstrated that these cytokines modulate the immunoresponse in Plasmodium falciparum malaria. The aim of this study was to measure the plasma levels of IL-12, IL-18 and TGF-beta in 105 African children with various degrees of malaria, and correlate the production of these cytokines with the severity of the disease. IL-12, IL-18 and TGF-beta levels were determined using enzyme-linked immunosorbent assay. The severity of malaria was established by parasitemia, clinical symptoms and haematological parameters. The levels of IL-12, IL-18 and TGF-beta were found to be significantly elevated (15.6 + / - 12.3, 22.7 + / - 13.8 pg/ml and 25.14 + / - 13.22 pg/ml respectively) in all of the children. IL-12 and IL-18 levels were significantly lower (13.2 + / - 5.53 and 21.5 + / - 10 pg/ml pg/ml) in children with severe disease, whereas the level of TGF-beta was higher (28.09 + / - 12.39 pg/ml). In contrast, IL-12 and IL-18 levels were found to be higher (17.32 + / - 7.8 pg/ml and 25.7 + / - 7.6 pg/ml) in patients with mild disease, whereas the level of TGF-beta was lower (20.92 + / - 12.76 pg/ml) compared to the severe malaria group. The correlation between IL-12 and IL-18 demonstrated a progressive relationship up to a value of IL-12 < 25 pg/ml, while IL-18 remained stable at higher levels of IL-12. An inverse correlation was found between IL-12 and TGF-beta up to a value of IL-12 < 30, after which the level of TGF-beta remained stable. This finding suggests that fine mechanisms regulate the interaction between IL-12, IL-18 and TGF-beta in the immune response to Plasmodium falciparum.     

Simultaneous measurement of multiple Th1 and Th2 serum cytokines in psoriasis and correlation with disease severity

BACKGROUND: Psoriatic plaques have been shown to contain increased levels of proinflammatory cytokines. Serum levels of interleukin (IL)-6, IL-7, IL-8, and interferon (IFN)-gamma have been reported elevated in psoriatic patients. AIM: To evaluate serum cytokine profiles in psoriasis patients by improved enzyme-linked immunosorbent assay (ELISA) technique and to correlate these levels with disease severity. METHODS: We analyzed single serum samples from 10 patients with active untreated psoriasis, two patients with active treated psoriasis, and five healthy volunteers for major T helper type 1 and T helper type 2 cytokines using the LINCOplex ELISA multi-analyte detection system that permits simultaneous detection of multiple cytokines from a single sample. The disease severity, including erythema, induration, scale, and surface area, was assessed. RESULTS: IFN-gamma was markedly elevated in all sera from psoriasis patients, 33.8 +/- 1.3 pg/ml (mean +/- standard error) versus 8 +/- 1.5 pg/ml for normal controls (p < 0.01), and positively correlated with all indices of disease severity (Spearman r > 0.6). IL-8 was also increased in psoriasis patients (24.4 +/- 1.8 pg/ml) versus normal controls (3.6 +/- 1.2 pg/ml) (p < 0.05) and positively correlated with the degree of erythema (Spearman r > 0.6). Mean IL-12 levels were decreased in sera from psoriasis patients (8.5 +/- 1.2 pg/ml) compared with normal controls (42.2 +/- 5.3 pg/ml) (p < 0.01). Also, serum IL-10 levels were below detection levels in psoriatics compared with controls (6.4 +/- 1.3 pg/ml). CONCLUSIONS: This new ELISA system allowed rapid and reliable detection of numerous cytokines in single serum samples from patients with psoriasis. We observed that IFN-gamma and IL-8 cytokines were elevated in psoriatics and correlated with parameters of disease severity while IL-10 and IL-12 were decreased.     

Effect of psoriasis activity on VEGF and its soluble receptors concentrations in serum and plaque scales

Vascular endothelial growth factor (VEGF) demonstrating pro-angiogenic activity promote new blood vessel formation in psoriatic lesions. The aim of this study was to evaluate the serum concentrations of VEGF, its soluble receptors (sVEGF R1 and R2) and VEGF content in scales of patients with psoriasis. To analyze possible association with activity of the disease, serum and scales from plaques were collected from 59 patients with exacerbated chronic plaque-type psoriasis. Mean concentrations of VEGF and sVEGF R1 in sera of patients were respectively two and four times higher than in healthy controls. Serum VEGF and sVEGF R1, but not sVEGF R2 demonstrated significant correlation with psoriasis area and severity index (PASI). There was also significant correlation between VEGF levels in serum and scales. Serum sVEGF R1 concentration was significantly elevated even in patients with low psoriasis activity (PASI<10), whereas increase of serum VEGF became significant in patients with medium activity (PASI: 10-20). Levels of serum VEGF and sVEGF R1 were the highest in patients with PASI>20. We confirmed association of both serum and scales VEGF concentrations with degree of psoriasis activity and demonstrated predominant increase of sVEGF R1 vs. VEGF in serum of patients with low psoriasis activity.     

Transforming growth factor beta1 and soluble Fas serum levels in hepatocellular carcinoma

In this study we assessed the usefulness of serum Transforming Growth Factor-beta1 (TGF-beta1) and soluble Fas (sFas) in distinguishing liver cirrhosis (LC) with and without hepatocellular carcinoma (HCC) as compared with alpha-fetoprotein (AFP). Serum TGF-beta1 and sFas levels were measured by ELISA in 51 LC patients, 54 patients with HCC and 30 healthy donors. Considering as a cut-off limit (mean+1SD of controls) 74 pg/ml and 637 pg/ml for TGF-beta1 and sFas, respectively, we computed serum concentrations of TGF-beta1 and sFas as a score (mean+/-SD). The positive frequency of serum TGF-beta1 levels in HCC patients (54%) was greater than in LC patients (26%) and healthy donors (3%). TGF-beta1 levels were higher in HCC (1.6+/-0.5) than in LC (1.1+/-0.2) (P<0.0001) and healthy donors (0.6+/-0.2). Using a cut-off limit of 82 pg/ml (mean+2SD), the positive frequency of TGF-beta1 was 20% in HCC patients. None of the controls and LC patients had TGF-beta1 levels higher than 82 pg/ml. The positive frequency of serum sFas levels was 100% in HCC patients, 98% in LC patients and 3% in healthy controls. Serum sFas levels were higher in HCC (2.5+/-0.7) than in LC (1.9+/-0.5) (P<0. 001) and healthy donors (0.6+/-0.3). No significant change of positive frequency was obtained by setting sFas cut-off at higher levels. sFas values did not correlate with TGF-beta1 levels. No relationship was found between TGF-beta1 amounts and AFP levels. However, in the 23% of HCC patients, with normal AFP values TGF-beta1 levels were higher than the cut off. These findings suggest the potential usefulness for TGF-beta1 assay in AFP-negative HCC.     

Effect of ulcerative colitis activity on plasma concentration of transforming growth factor beta1

Enhanced expression of transforming growth factor-beta1 (TGF-beta1) demonstrated in human colonic mucosa of patients with ulcerative colitis (UC), indicates its possible significance in the pathogenesis of this disease. The aim of this study was to evaluate plasma TGF-beta1 concentration in patients with different degrees of colonic mucosal injury, as a possible indicator of ulcerative colitis activity. TGF-beta1 concentration was measured with an enzyme immunoassay (EIA) in plasma of 45 patients with endoscopically confirmed UC. Values observed in UC patients (40.5+/-15.9 ng/ml) were significantly higher than in healthy people (18.3+/-11.6 ng/ml) and higher than in patients with irritable colon syndrome (ICS), (20.5+/-13.6 ng/ml). The highest plasma TGF-beta1 (58.6+/-112.1 ng/ml) was in patients with the severe UC course. TGF-beta1 level analysed in all UC patients revealed significant positive correlation with scored degree of mucosal injury (r=0.396;P<0.01). Among other possible laboratory markers of the disease activity, only C-reactive protein concentration demonstrated significant correlation. Enhanced production of TGF-beta1 can be related to inflammation activity. Measurement of plasma TGF-beta1 may be considered as a biomarker of the disease activity.     

Psoriasis decreases the anti-oxidation and anti-inflammation properties of high-density lipoprotein

Psoriasis is a chronic inflammatory skin disease, which has been linked to dyslipidemia with potential functional impairment of lipoproteins. This cross-sectional study was designed to characterize the biological activities of plasma lipoproteins in 25 patients with psoriasis and 25 age- and sex-matched healthy controls.In the present study, we found that plasma levels of high-density lipoprotein (HDL) cholesterol were decreased in the psoriasis group compared to healthy controls. The malondialdehyde (MDA) content in plasma, in HDL3 and in low-density lipoprotein (LDL) were increased. However, the activity of plasma paraoxonase-1 (PON-1) decreased in psoriasis and negatively correlated with the psoriasis area and severity index (PASI). Moreover, plasma levels of tumor necrosis factor-α (TNF-α) and interleukin-6 (IL-6) were increased in psoriasis and positively correlated with the PASI. High-sensitivity C-reactive protein (hs-CRP) was increased in psoriasis, but did not reach significance when correlated with PASI. In vitro tests displayed that the functionalities of HDL3 isolated from psoriatic patients significantly decreased, which were assessed in four independent ways, namely (1) protection against LDL oxidation, (2) inhibition of tumor necrosis factor-α (TNF-α) induced monocyte adherence to endothelial cells, (3) prevention of oxidized low density lipoprotein (ox-LDL) induced monocyte migration, and (4) protection of endothelial cells from TNF-α induced apoptosis. Further, pro-oxidative and pro-inflammatory properties of LDL isolated from psoriatic patients were increased. In conclusion, the biological activities of psoriatic lipoproteins are impaired in both HDL and LDL, which may provide a link between psoriasis and cardiovascular disease.     

Effect of psoriasis activity on VEGF and its soluble receptors concentrations in serum and plaque scales

Vascular endothelial growth factor (VEGF) demonstrating pro-angiogenic activity promote new blood vessel formation in psoriatic lesions. The aim of this study was to evaluate the serum concentrations of VEGF, its soluble receptors (sVEGF R1 and R2) and VEGF content in scales of patients with psoriasis. To analyze possible association with activity of the disease, serum and scales from plaques were collected from 59 patients with exacerbated chronic plaque-type psoriasis. Mean concentrations of VEGF and sVEGF R1 in sera of patients were respectively two and four times higher than in healthy controls. Serum VEGF and sVEGF R1, but not sVEGF R2 demonstrated significant correlation with psoriasis area and severity index (PASI). There was also significant correlation between VEGF levels in serum and scales. Serum sVEGF R1 concentration was significantly elevated even in patients with low psoriasis activity (PASI < 10), whereas increase of serum VEGF became significant in patients with medium activity (PASI: 10–20). Levels of serum VEGF and sVEGF R1 were the highest in patients with PASI > 20. We confirmed association of both serum and scales VEGF concentrations with degree of psoriasis activity and demonstrated predominant increase of sVEGF R1 vs. VEGF in serum of patients with low psoriasis activity.     

Effect of estradiol-17beta on PGF and total protein content in bovine uterine flushings and peripheral plasma concentration of 13, 14-dihydro-15-keto-PGF(2alpha)

Two experiments were conducted to examine the effect of estradiol-17beta (E(2)-17beta) on content of immunoreactive prostagladin F(2)alpha (PGF, ng) and total protein (TUP, mg) in uterine flushings, as well as concentrations of 13, 14-dihydro-15-keto-PGF(2)alpha (PGFM) in plasma (Pg/ml). In experiment 1, Holstein heifers were utilized in a single reversal trial in which either E(2)-17beta (3 mg in 2 ml saline/ethanol 50:50; n=5) or vehicle alone (n=6) were given intravenously on day 14 or 15 of the estrous cycle (Period 1) following an induced estrus (day of estrus = day 0). Treatment (Trt) groups were reversed in Period 2 (Day 14 or 15 of the second estrous cycle). Jugular venous plasma was obtained before treatment (Oh), and at 5, 6, and 9h posttreatment (PT). Uterine flushings were collected nonsurgically in vivo , per cervix, via Foley catheter at 6h PT (20 ml of .9% saline per uterine horn). E(2)-17beta did not significantly alter (E(2)-17beta vs vehicle; x(-) +/- S.E.M.) PGF (1674 +/- .11 +/- 338.39 vs 1889.91 +/- 400.24 ng; P> .10) or TUP (33.25 +/- 2.57 vs 39.16 +/- 3.04 mg; P > .10). However, E(2)-17beta increased (P < .05) plasma PGFM (E(2)-17beta vs vehicle) after treatment (0h, 113.2 vs 163.8; 5h, 312.5 vs 203.9; 6h, 324.5 vs 198.0; 9h, 323.2 vs 246.8, pg/ml). In experiment 2, crossbred beef cattle received comparable treatments of either E(2)-17beta (n=5) or vehicle (n=5) on day 14 or 15 postestrus. Jugular venous plasma was obtained at 0h PT, and at 6h PT. Uterine flushings (1.9% saline, 20 ml per uterine horn) and peripheral plasma were collected at slaughter. Estradiol-17beta increased PGF (30.07 +/- 5.94 vs 8.46 +/- 2.01 ng; P> <.05) in uterine flushings as well as PGFM in plasma (E(2)-17beta : 55.82 +/- 19.13 pg/ml, at 0h and 89.31 +/- 14.02 pg/ml, at 6h, vs saline: 103.46 +/- 50.73 pg/ml, at 0h and 17.78 +/- 14.22, at 6h). Estradiol-17beta stimulated uterine production and release of PGF and protein as measured in flushings (experiment 2) as well as plasma PGFM responses (experiments 1 and 2). Uterine and/or cervical stimulation of experiment 1 may have masked uterine response to E(2)-17beta.     

Circulating transforming growth factor beta(1) as an indicator of hepatic function impairment in liver cirrhosis

In the liver, transforming growth factor (TGF) -beta(1)is primarily responsible for activation of fat-storing cells, which are the main source of extracellular matrix proteins. Their deposition play a key role in the development of liver cirrhosis. The aim of this study was to evaluate plasma TGF-beta(1)in patients with different stages of liver cirrhosis and its possible use as an indicator of liver function impairment. TGF-beta(1)was measured in the plasma of 40 patients with liver cirrhosis. To estimate possible effect of liver insufficiency on plasma TGF-beta(1), patients were divided into three groups: A, B and C, univocal with Child-Pugh classes. Normal values were collected from 13 healthy volunteers. Liver cirrhosis resulted in a significant increase of plasma concentration of TGF-beta(1)(39.3+/-3.8 ng/ml), which doubled normal values (18.3+/-1.6 ng/ml). The highest concentrations were observed in alcoholic patients (44.4+/-4.7 ng/ml). TGF-beta(1)level increased depending on the degree of liver insufficiency, demonstrated by a significant positive correlation with Child-Pugh score (r=0.591). Values in group A were similar to normal, but were significantly elevated in groups B and C. These findings suggest possible use of plasma TGF-beta(1)measurement as an indicator of liver function impairment and possible marker of hepatic fibrosis progression in cirrhotic patients.     

Increased plasma macrophage inflammatory protein (MIP)-1alpha and MIP-1beta levels in type 1 Gaucher disease

Pancytopenia, hepatosplenomegaly and skeletal complications are hallmarks of Gaucher disease. Monitoring of the outcome of therapy on skeletal status of Gaucher patients is problematic since currently available imaging techniques are expensive and not widely accessible. The availability of a blood test that relates to skeletal manifestations would be very valuable. We here report that macrophage inflammatory protein (MIP)-1alpha and MIP-1beta, both implicated in skeletal complications in multiple myeloma (MM), are significantly elevated in plasma of Gaucher patients. Plasma MIP-1alpha of patients (median 78 pg/ml, range 21-550 pg/ml, n=48) is elevated (normal median 9 pg/ml, range 0-208 pg/ml, n=39). Plasma MIP-1beta of patients (median 201 pg/ml, range 59-647 pg/ml, n=49) is even more pronouncedly increased (normal median 17 pg/ml, range 1-41 pg/ml, n=39; one outlier: 122 pg/ml). The increase in plasma MIP-1beta levels of Gaucher patients is associated with skeletal disease. The plasma levels of both chemokines decrease upon effective therapy. Lack of reduction of plasma MIP-1beta below 85 pg/ml during 5 years of therapy was observed in patients with ongoing skeletal disease. In conclusion, MIP-1alpha and MIP-1beta are elevated in plasma of Gaucher patients and remaining high levels of MIP-1beta during therapy seem associated with ongoing skeletal disease.     

Wide-spectrum profile of inflammatory mediators in the plasma and scales of patients with psoriatic disease

Psoriasis is a chronic recurrent inflammatory disorder of the skin. Clinical subtypes include psoriasis vulgaris (PV), psoriatic arthropathy, and erythrodermic psoriasis. Aim of this study was to analyse relevant inflammatory mediators in the plasma of patients with distinct subtypes of active psoriasis, and in the scales of mild-to-moderate PV patients, and correlation to disease severity. Compared to healthy controls (n = 10), patients affected by very severe forms of psoriasis (n = 30) were characterized by increased plasma levels of IL-4, IL-6, MCP-1, VEGF and in particular PDGFbb. Each group with severe psoriasis had distinct characteristic features of plasma cytokine profile. Mild-to-moderate PV patients (n = 35) showed higher levels of IL-4, IL-6, IL-10, and IL-13 when compared to healthy controls. No correlation was found between PV severity assessed by PASI (Psoriasis Area and Severity Index) and levels of these mediators. By contrast, disease severity correlated to scale levels of IP-10. For the first time, we found exaggerated circulating levels of the pro-angiogenic PDGFbb and VEGF in severe psoriasis. Evidence that the severity of skin symptoms correlated exclusively with scale levels of IP-10, but not with any up-regulated inflammatory mediator in plasma, suggests that distinct skin-independent processes contribute to the circulating cytokine profile in psoriasis.     

Transforming growth factor beta 1 serum levels in patients with preinvasive and invasive lesions of the breast

Transforming growth factor beta (TGF-beta)1 is thought to be involved in breast carcinogenesis. TGF-beta1 acts in an antiproliferative manner in the early stages of breast carcinogenesis, but promotes tumor progression and metastases in the advanced stages of the disease. No data have been published on serum TGF-beta1 in breast cancer. We investigated TGF-beta1 serum levels in patients with breast cancer (n=135), ductal carcinoma in situ (DCIS) I to III (n=67) or fibroadenoma (n=35), and in healthy women (n=40) to determine its value as a differentiation marker between malignant, pre-invasive and benign diseases and as a predictive marker for metastatic spread. Median (range) TGF-beta1 serum levels in patients with breast cancer, DCIS I-III or benign breast lesions and in healthy women were 48.8 (18-82.4) pg/mL, 45.3 (26.9-58.3) pg/mL, 47.2 (17.2-80.5) pg/mL and 51.6 (30.9-65.1) pg/mL, respectively (p=0.2). In breast cancer patients TGF-beta1 serum levels showed no statistically significant correlation with tumor stage, lymph node involvement, histological grade, estrogen receptor status and progesterone receptor status. Our data fail to indicate any correlation between serum TGF-beta1 levels and clinicopathological parameters of breast diseases. Serum TGF-beta1 levels do not provide clinical information in addition to established tumor markers.     

Differential levels of soluble endoglin (CD105) in myeloid malignancies

Angiogenesis contributes to disease progression in solid and hematopoietic malignancies, and endoglin (CD105), a component of the transforming growth factor (TGF)-beta receptor complex, is a powerful marker of neovascularization. Elevated amounts of soluble CD105 (sCD105) have been recently identified in selected solid tumors but no data are available on sCD105 in hematopoietic malignancies. Therefore, levels of sCD105 were investigated in sera of patients with acute myeloid leukemia (AML) (n = 10) or chronic myeloproliferative disorders (CMD) (n = 28), and correlated with those of soluble TGF-beta(1) (sTGF-beta(1)). Dot blot assay detected higher amounts of sCD105 (P < 0.05) both in AML (4.34 +/- 2.62 OD/mm(2)) and in CMD (3.71 +/- 2.09 OD/mm(2)) patients than in healthy subjects (n = 14, 2.38 +/- 1.18 OD/mm(2)). Instead, enzyme-linked immunosorbent assay (ELISA) identified (P < 0.05) lower and higher levels of sTGF-beta(1) in AML (32,017 +/- 1,900 pg/ml) and CMD (60,700 +/- 19,200 pg/ml) patients, respectively, compared to healthy individuals (n = 11, 47,173 +/- 5,443 pg/ml). In essential thrombocythemia (ET) patients with thrombotic episodes, levels of sCD105 were lower (P < 0.05) compared to patients without thrombotic complications, and inversely correlated with those of sTGF-beta(1) (r = 0.94). Conversely, amounts of sCD105 directly correlated with levels of sTGF-beta(1) (r = 0.74) in ET patients without thrombotic events. Our results show that high levels of sCD105 are present in myeloid malignancies that are characterized by a high cellular proliferation rate, and suggest that an altered balance between sCD105 and sTGF-beta(1) might favor disease progression and clinical complications.     

Circulating angiogenic cytokines in multiple myeloma and related disorders

We investigated the serum concentrations of selected angiogenic cytokines including: vascular endothelial growth factor (VEGF), hepatocyte growth factor (HGF), transforming growth factor beta 1 (TGF-beta1) and basic fibroblast growth factor (bFGF) in 162 patients with multiple myeloma (MM), 5 patients with Waldenstr m's macroglobulinaemia (WM), and 31 healthy controls. Among the MM patients there were 2 cases of primary plasma cell leukemia (PCL) and one case of extramedullary plasmacytoma. The levels of measured cytokines were correlated with the phase and stage of the disease as well as the most important clinical and laboratory parameters associated with disease activity (haemoglobin, creatinine, albumins, calcium, M-component, CRP,beta2m, LDH and bone involvement). We have found correlations between serum levels of angiogenic cytokines and some parameters depicting the disease activity and advancement. The serum level of VEGF in MM patients (median 244.5 pg/mL) correlated with serum concentrations of beta-2-microglobulin (beta2m) greater than 2.5 mg/L (p = 0.0005) and abnormal values of lactate dehydrogenase (> 425 U/L, median 329.0 pg/mL and < 210 U/L, median 426.6 pg/mL, p = 0.004 and p = 0.04 respectively). MM patients in stage III had higher serum levels of HGF (median 1 411.3 pg/mL) than those in stage I (median 1 219 pg/mL) (p = 0.01) according to Durie and Salmon staging, and those in phase I (at diagnosis) (median 1 555.6 pg/mL) and phase III (in progression) (median 1 309.7 pg/mL) had higher levels than those in phase II (plateau phase) (median 1 047.9 pg/mL) (p = 0.002 and p = 0.02 respectively). Significantly elevated values of HGF were found in MM patients with anaemia (median 1 962.0 pg/mL) and hypercalcaemia (median 2 085.6 pg/mL) (p = 0.00001 and 0.04 respectively). TGF-beta1 (median 33.9 ng/mL) correlated positively with highbeta2m values (> 2.5 mg/L) (p = 0.04) and was significantly higher in phase I (median 40.1 ng/mL) than in phase II (median 30.9 ng/mL) (p = 0.03) of the disease. The concentration of bFGF was significantly higher in stage III of MM (median 3.1 pg/mL) than in stage I (median 1.2 pg/mL) (p = 0.04). We found that the survival probability was statistically higher for newly diagnosed MM patients with a concentration of VEGF lower than the median value for this cytokine. The concentrations of the cytokines analyzed in patients with Waldenstr m's macroglobulinaemia (WM), primary plasma cell leukaemia (PCL) and non-secretory (NS) myeloma were not distinguishable from those found in MM patients. We also studied the relationship between the levels of cytokines analyzed and found positive correlations between bFGF and TGF-beta1 (rh? = 0.183, p < 0.02), as well as VEGF and TGF-beta 1 (rh? = 0.537, p < 0.001) and VEGF and bFGF (rh? = 0.197, p < 0.02). In conclusion, our data indicate a strong relationship between angiogenic cytokine serum levels and clinical course as well as selected laboratory parameters of patients with MM.     

TGF-beta(1) gene polymorphism in psoriasis vulgaris

Overexpression of TGF-beta(1) has been implicated in the pathology of many inflammatory diseases, including psoriasis. This study was performed to investigate the association between TGF-beta(1) single nucleotide polymorphism and susceptibility for psoriasis vulgaris. DNA from 78 patients with psoriasis vulgaris and 74 healthy volunteers was investigated. Polymorphism of TGF-beta(1) gene in codon 10 (T/C) and codon 25 (G/C) was evaluated by PCR-SSP and the results were compared between group of psoriatic patients, divided into early onset of psoriasis (type I) and late onset of psoriasis (type II) subgroups, and control healthy subjects. Frequencies in genotypes were similar between patients and control group (p >0.7), but between type I and type II psoriasis patients highly significant difference was found (p <0.0003). Higher frequency of CC/GG (intermediate producer) and TC/GG (high producer) was noted in the type I group, but the second high producer genotype (TT/GG) was more common in type II group. Also between type II psoriasis patients and healthy controls statistically significant difference was found (p <0.000001). In analyzing frequencies of carriage and alleles no significant differences were found. TGF-beta(1) gene polymorphism in codon 10 and 25 is not associated with susceptibility to psoriasis vulgaris, but may be important for the type of the disease.