Ugur Musabak

Pro- and anti-inflammatory cytokine balance in major depression: effect of sertraline therapy.

The specific associations between antidepressant treatment and alterations in the levels of cytokines remain to be elucidated. In this study, we aimed to explore the role of IL-2, IL-4, IL-12, TNF-α, TGF-β1, and MCP-1 in major depression and to investigate the effects of sertraline therapy. Cytokine and chemokine levels were measured at the time of admission and 8 weeks after sertraline treatment. Our results suggest that the proinflammatory cytokines (IL-2, IL-12, and TNF-α) and MCP-1 were significantly higher, whereas anti-inflammatory cytokines IL-4 and TGF-β1 were significantly lower in patients with major depression than those of healthy controls. It seems likely that the sertraline therapy might have exerted immunomodulatory effects through a decrease in the proinflammatory cytokine IL-12 and an increase in the anti-inflammatory cytokines IL-4 and TGF-β1. In conclusion, our results indicate that Th1-, Th2-, and Th3-type cytokines are altered in the depressed patients and some of them might have been corrected by sertraline treatment.

Systemic Markers of Lipid Peroxidation and Antioxidants in Patients with Nonalcoholic Fatty Liver Disease

OBJECTIVES:The aim of the present study was to examine the systemic parameters of oxidative stress and antioxidants in patients with nonalcoholic fatty liver disease and investigate the relationship between these parameters and clinical and biochemical outcomes.METHODS:Fifty-one male patients with nonalcoholic fatty liver disease (group I), 30 age-matched and body mass index (BMI)-matched healthy male subjects, and 30 age-matched male patients with chronic viral hepatitis (group II) were enrolled in the study.RESULTS:Increased systemic levels of malondialdehyde and depletion of antioxidants such as coenzyme Q10, CuZn-superoxide dismutase, and catalase activity were observed in group I. Coenzyme Q10 and CuZn-superoxide dismutase correlated negatively with increasing necroinflammatory activity and fibrosis. Body fat was negatively associated with plasma coenzyme Q10 levels, while an inverse association was found between plasma catalase levels and TG. However, LDL was positively associated with plasma malondialdehyde levels. CuZn-superoxide dismutase levels were negatively associated with glucose, insulin, and HOMA-IR. In addition, the levels of CuZn-superoxide dismutase correlated significantly in a negative manner with BMI.CONCLUSIONS:Our results concerning correlations suggest that disturbances in BMI, body fat, and lipid metabolism may contribute to altered oxidative status in NAFLD, and insulin resistance may be related to decreased antioxidants in NAFLD as well as products of lipid peroxidation. However, although our results suggest interesting correlations, this different mostly “weak” relationships must be taken with caution.

Serum interleukin-18 levels in patients with Behçet’s disease. Is its expression associated with disease activity or clinical presentations?

Interleukin (IL)-18 is a proinflammatory cytokine which plays a crucial role in T helper (Th)1 type immune response. The aim of this study is to investigate the relationship of serum levels of IL-18 with disease activity and clinical presentations in patients with Behcet’s disease (BD). Sixty patients with BD and 20 healthy controls were included in the study. Patients were grouped as having active or inactive disease according to the Leeds activity score. They were also separated as a systemic involvement or mucocutaneous symptoms only. Patients with systemic involvement were further grouped according to the presence of ocular, articular and vascular involvement. IL-18 levels were significantly higher in all patient subgroups as compared to healthy controls and found to be correlated with the activity score in patients having active disease. In conclusion, this cytokine participates in the pathogenesis of BD and its levels are correlated with the disease activity. Detection of increased levels of IL-18 in patients with inactive disease implies that Th1 activation and subclinical inflammation persist during the inactive period of the disease.

Synovial proinflammatory cytokines and their correlation with matrix metalloproteinase-3 expression in Behçet’s disease. Does interleukin-1β play a major role in Behçet’s synovitis?

The objective of this study has been the well established fact that proinflammatory cytokines and metalloproteinases play a crucial role in the pathogenesis of chronic arthritis as well as the development of pannus, with the eventual erosive changes. Among the proinflammatory cytokines, interleukin-18 (IL-18) has been shown to contribute to the pathogenesis of chronic synovitis by increasing the secretion of interleukin-1beta (IL-1β) and the tumor necrosis factor-alpha (TNF-α) and also stimulating angiogenesis. The aim of this study is to investigate the synovial IL-18, IL-1β, TNF-α and matrix metalloproteinase-3 (MMP-3) levels in patients with Behçet’s disease (BD), and compare them with the levels of patients with rheumatoid arthritis (RA) and osteoarthritis (OA). 30 patients with BD, 20 with RA, and 20 with OA were included in the study. The synovial levels of IL-18, IL-1β, TNF-α and MMP-3 were detected using the two-step sandwich ELISA method. The synovial IL-18, TNF-α and MMP-3 levels were significantly higher in RA patients than patients with BD (P=0.004, 0.019, 0.025, respectively) and with OA (P=0.004, 0.045, 0.032, respectively). There were no differences, with respect to the cytokine levels, when patients with BD were compared with those with OA. Patients with RA and BD had higher IL-1β levels than patients with OA (P=0.017, 0.013, respectively). However, no such difference was found for IL-1β between BD and RA patients. Among patients with RA, positive correlations were found between TNF-α and MMP-3 (r=0.683, P=0.001). Our results showed that MMP-3 and proinflammatory cytokines, except IL-1β, were expressed in relatively small quantities in Behçet’s synovitis. Detection of the lower levels of these cytokines and metalloproteinases might explain the non-erosive character of Behçet’s arthritis. We suggest that IL-1β may be involved in the pathogenesis of Behçet’s synovitis.

Serum Adiponectin, TNF-α, IL-12p70, and IL-13 Levels in Multiple Sclerosis and the Effects of Different Therapy Regimens

Objectives: Multiple sclerosis (MS) is a chronic inflammatory disease of the human central nervous system. In the present study, we aimed to determine adiponectin, tumor necrosis factor-α, interleukin (IL)-12p70, and IL-13 levels in the sera of patients with MS and to investigate the effects of interferon (IFN), glatiramer acetate (GA), and immunosuppressive treatment regimens on these parameters. Methods: Fifty-seven patients with MS and 34 healthy controls were enrolled into the study. Serum cytokine levels were measured using enzyme immunoassay. Results: Significantly elevated levels of IL-12p70 and IL-13 were found in the sera of patients with MS, but decreased adiponectin levels were found in patients’ sera compared to healthy controls. The levels of IL-12p70 and IL-13 in the IFN therapy group were higher than those of the healthy controls. However, the IL-12p70 and IL-13 levels in the GA therapy group were not different from those of the healthy controls. There were no differences with regard to adiponectin levels among the subgroups of patients with MS according to therapy regimen and the healthy controls. At the end of a 2-year follow-up period, Expanded Disability Status Scale (EDSS) values were found to be increased in the IFN therapy group but unchanged in the GA therapy group. Conclusions: These findings suggest that adiponectin, IL-12p70, and IL-13 may play a role in the pathogenesis of MS. Additionally, GA therapy regimens in MS are more effective than IFN therapy with respect to decreasing the levels of IL-12p70 and IL-13 and stabilizing the EDSS value.

Do the Changes in the Serum Levels of IL-2, IL-4, TNFα, and IL-6 Reflect the Inflammatory Activity in the Patients with Post-ERCP Pancreatitis?

Background. Acute pancreatitis is the major complication of endoscopic retrograde cholangiopancreatography (ERCP) procedure and there are some reports showing cytokine changes in ERCP-induced pancreatits. Goals. To investigate the association between early changes (within 24 hours) in the serum interleukin (IL)-2, IL-4, tumor necrosis factor (TNF)α, and IL-6 levels and the development of post-ERCP pancreatitis. Study. Forty five consecutive patients who underwent therapeutic ERCP and 10 patients with acute pancreatitis without ERCP were enrolled to the study. Serum concentrations of IL-2, IL-4, TNFα, and IL-6 were determined immediately before, 12 hours and 24 hours after ERCP. Results. Seven of the 45 patients (15.5%) developed post-ERCP pancreatitis. The levels of IL-4 at 24 hours after ERCP were significantly lower in the patients with post-ERCP pancreatitis than in those without pancreatitis, while TNFα levels at 12 hours after ERCP were higher in the complicated group than those of the uncomplicated group. The ratios of TNFα/IL-4 at 12 and 24 hours after ERCP were found significantly higher in the patients with post-ERCP pancreatitis than in those without pancreatitis. IL-6 in the complicated patients was found significantly increased at 24 hours after ERCP. Conclusions. The enhancement of serum TNFα and IL-6 levels in the patients with ERCP-induced pancreatitis reflects the inflammatory activity. Additionally, these cytokines together with IL-4 can be used in clinical laboratory monitoring of ERCP.

Study of Autoimmunity in Klinefelter's Syndrome and Idiopathic Hypogonadotropic Hypogonadism

Sex hormones play an important role in determining the progression and severity of autoimmune diseases, but the in vivo mechanisms underlying this relation are poorly understood. The main objective of current study has been to compare the changes in neuroendocrine immune features and autoantibody profile in male patients with hypogonadotropic and hypergonadotropic hypogonadism, and to determine the relationships between sex hormones and immunologic parameters. Thirty-seven male patients with Klinefelters syndrome and 35 men with idiopathic hypogonadotropic hypogonadism who had no history of previous hormonal therapy and 30 healthy men were recruited in the study. Serum autoantibody profile, sex hormones, and immunologic parameters were studied. In conclusion, our findings suggest that both humoral and cellular immunity is enhanced in male hypogonadism. Klinefelters syndrome patients also had increased frequency of antiextractable nuclear antibodies and anticardiolipin antibodies positivity compared to idiopathic hypogonadotropic hypogonadism patients. It is possible that testosterone deficiency and increased levels of estradiol are primary responsible factors for this enhanced autoantibody production in Klinefelters syndrome patients.

Omalizumab as a Steroid-Sparing Agent in Chronic Eosinophilic Pneumonia

Chronic eosinophilic pneumonia (CEP) is an idiopathic eosinophilic pulmonary disease characterized by an abnormal and marked accumulation of eosinophils in the lung. Common presenting complaints include cough, fever, dyspnea, wheezing, and night sweats. Common laboratory abnormalities are peripheral blood and BAL eosinophilia. The pathognomonic radiographic finding is bilateral peripheral infiltrates. Corticosteroids are the mainstay of therapy, and dramatic improvement follows treatment. Relapses are common, and most patients require prolonged therapy. Side effects associated with chronic corticosteroid therapy must be monitored. Our case was that of a 36-year-old woman who had characteristic clinical and radiologic features. She was treated with corticosteroids but she needed prolonged therapy, and side effects occurred. Because the patient had high IgE levels and a positive skin prick test result, we used omalizumab for the treatment. The patient responded well. To our knowledge, this is the first CEP case in the literature successfully treated with omalizumab.

Hyperhomocysteinemia in patients with Behçet’s disease: is it due to inflammation or therapy?

Considerable discrepancies exist in the literature with respect to plasma total homocysteine (tHcy) levels in Behçet’s disease (BD). The aim of this study was to evaluate tHcy concentrations in these patients. Thirty-two patients with BD and 20 age- and body mass index-matched healthy volunteers were enrolled. Plasma tHcy concentrations were significantly higher, while vitamin B12 and folate levels were significantly lower in patients with thrombosis and eye involvement than those without. C-reactive protein levels also correlated significantly in a negative manner with vitamin B12 and folate but positively with tHcy. In conclusion, increased use or accelerated catabolism of folate and vitamin B12 due to chronic inflammation and moderately increased tHcy concentrations related with deficiency of these cofactors, and immunosuppressive drug administration might be potential threats of vascular disease in BD.

Tissue levels of adiponectin, tumour necrosis factor-alpha, soluble intercellular adhesion molecule-1 and heart-type fatty acid-binding protein in human coronary atherosclerotic plaques

Background  There is little information available about any link between the levels of adiponectin, intercellular adhesion molecule‐1 (ICAM‐1), tumour necrosis factor‐α (TNF‐α) and heart‐type fatty acid‐binding protein (H‐FABP) in coronary atherosclerotic plaque specimens.