ABSTRACT
OBJECTIVES: To evaluate serum levels of fractalkine (FKN), a mediator of leukocyte transmigration, C-reactive protein (CRP) and expression of integrins CD11a and CD49d on peripheral blood lymphocytes in systemic sclerosis (SSc) and to investigate whether they are modulated by intravenous prostaglandin E1 (PGE1). METHODS: Serum levels of fractalkine and C-reactive protein and expression of CD11a and CD49d on peripheral blood lymphocytes were assessed in 50 SSc patients and in 18 healthy controls. In 25 SSc patients studied parameters were evaluated also after 3 consecutive daily PGE1 infusions (20 microg-40 microg-60 microg) and after 4 weeks. RESULTS: In SSc fractalkine basal level was significantly higher than in controls (9.04+/-1.79 ng/ml vs. 1.17+/-0.1 ng/ml; p<0.0001) and decreased significantly after PGE1 (5.16+/-1.27 ng/ml, p<0.05). After four weeks fractalkine level was still significantly lower than baseline 7.70+/-2.19 ng/ml (p<0.05). Basal percentage of CD11a (+) nor CD49d (+) lymphocytes in SSc (82.38+/-1.60%, 70.74+/-1.68%, respectively) did not differ from controls (85.73+/-2.04%, 75.62+/-2.48%; respectively, p>0.05). PGE1 treatment resulted in decrease of both CD11a (+) (67.72+/-3.34%, p<0.0001) and CD49d (+) lymphocytes (65.32+/-1.62%, p<0.0001). After 4 weeks the percentage of CD11a (+) and CD49d (+) lymphocytes remained significantly lower than at baseline (77.80+/-2.47% and 65.32+/-1.62%, respectively, both p<0.001). In SSc CRP basal level was significantly higher than in controls (4.70+/-2.01 mg/dl vs. 1.40+/-1.79 mg/dl, p<0.005) and reduced significantly after PGE1 (3.39+/-2.06 mg/dl, p<0.05). After 4 weeks, CRP level (4.38+/-2.19 ng/ml) was significantly lower than baseline (p<0.05). CONCLUSION: Fractalkine may play an important role in the pathogenesis of vascular dysfunction in systemic sclerosis. Prostaglandin E1 down-regulates serum fractalkine level, as well as CD11a and CD49d expression on peripheral blood lymphocytes, which suggests additional mechanisms in which this vasodilatatory agent exerts its efficacy in systemic sclerosis.
Subject(s)
Alprostadil/administration & dosage , Chemokine CX3CL1/blood , Scleroderma, Diffuse/drug therapy , Scleroderma, Limited/drug therapy , Vasodilator Agents/administration & dosage , Adult , C-Reactive Protein/analysis , C-Reactive Protein/drug effects , CD11a Antigen/drug effects , CD11a Antigen/metabolism , Case-Control Studies , Chemokine CX3CL1/drug effects , Down-Regulation , Female , Humans , Infusions, Intravenous , Integrin alpha4/drug effects , Integrin alpha4/metabolism , Lymphocytes/drug effects , Lymphocytes/metabolism , Male , Middle Aged , Scleroderma, Diffuse/blood , Scleroderma, Limited/bloodABSTRACT
Leptin, a peptide hormone, plays an essential role in the regulation of body weight, the endocrine function, reproduction, the immune response and inflammation. The immune system, in turn, modifies leptin's production. Systemic lupus erythematosus (SLE) is an autoimmunological disease characterized by widespread inflammation with possible involvement of each body organ and system. In this study, we assessed serum leptin levels in SLE patients and the control group in search for correlations between leptin concentrations and other markers' level, the activity of the disease, its duration, the age of the patients and their bone mineral density. Blood samples were collected from 30 SLE and 30 control group women. Each SLE patient was matched with one from the control for age (+/-1 year) and the body mass index (BMI; +/-1). Serum leptin levels were determined using the DRG Leptin ELISA Kit. Serum leptin levels in SLE patients ranged from 1.8 to 66.3 ng/ml (median value 7.5), and in control group it was 8.8 ng/ml (0.7-39.2) (NS). In SLE, serum leptin levels (after the logarithmic transformation) correlated with BMI (r = 0.89, P < 0.0001), the age (r = 0.34, P < 0.01) and the patients' disease duration (r = 0.59, P < 0.0005). Serum leptin levels in SLE patients with arthritis (P < 0.05) and central nervous system (CNS) involvement (P = 0.05) were significantly lower in comparison with serum leptin levels in SLE patients without arthritis and CNS involvement. No correlation was found between serum leptin levels and the T-score. In the control group, the logarithmic transformation of serum leptin levels positively correlated with BMI (r = 0.52, P < 0.05). No differences in serum leptin levels were shown between SLE patients and the control group. However, we found correlation between BMI and serum leptin levels in both groups. Furthermore, serum leptin levels in SLE patients with arthritis and CNS involvement were significantly lower in comparison with SLE patients without arthritis and CNS involvement, which suggests that active chronic inflammation may lower plasma leptin concentrations.
