allopurinol and Behcet-Syndrome

Behçet's disease (BD) is a multisystem disease, which shares some features with other diseases belonging to the autoinflammatory disorders panel. Recent studies have postulated that IL-1β/Caspase-1 may play a cardinal role in autoinflammatory diseases. In this study, we aimed to (i) elucidate the mechanism underlying the involvement of xanthine oxidase (XO) and Uric Acid (UA) in BD (ii) study the direct effects of UA and XO inhibitor "Allopurinol" on nitric oxide (NO) and caspase-1-mediated IL-1β release in peripheral blood mononuclear cells (PBMCs) of BD patients. In this context, plasma of BD patients and healthy controls (HC) were used to measure XO activity, UA, advanced oxidized proteins products (AOPP) and NO levels. In Addition, PBMCs of BD patients and HC were treated or not with either UA or Allopurinol. Then we quantified NO and IL-1β levels, and Caspase-1 Activity in the supernatants and lysates of PBMCs, respectively. We showed that plasma levels of XO activity, UA, AOPP and NO are significantly increased in BD patients compared to those of HC. Interestingly, a significant positive correlation between XO and UA was observed in BD patients. Additionally, while UA has markedly increased NO, IL-1β, and Caspase-1 activity levels in PBMCs of BD patients, Allopurinol has exerted an immunomodulatory effect resulting in reduced NO, IL-1β and Caspase-1 levels in PBMCs of BD patients particularly during the active stages. Collectively, our results indicate a potential clinical use of XO as a tool for assessing BD activity, and suggest that the in-vitro immunomodulatory effect of Allopurinol may have a promising therapeutic value in BD management.

Topics: Adult; Allopurinol; Behcet Syndrome; Caspase 1; Cells, Cultured; Female; Humans; Immunologic Factors; Interleukin-1beta; Leukocytes, Mononuclear; Male; Middle Aged; Nitric Oxide; Uric Acid; Xanthine Oxidase; Young Adult

Adenosine deaminase (AD) and xanthine oxidase (XO) are enzymes of purine catabolism that catalyze the conversion of adenosine to inosine, deoxyadenosine to deoxyinosine, hypoxanthine to xanthine and xanthine to uric acid, respectively. AD is known to be an important enzyme in the maturation and function of T lymphocytes. The aim of this prospective study was to evaluate whether there are changes in serum AD activity as an index of T lymphocyte function in Behcet's disease (BD) which is known as having T cell-mediated immune response.. A total of 32 patients and 26 sex- and age-matched healthy control subjects were analysed for AD and XO activities. The patients with BD were divided into two subgroups: BD with and without eye lesions. Twelve patients with complete BD and four patients with incomplete BD had eye complications. AD and XO activities in serum were measured with spectrophotometric methods.. There was a remarkable increase in AD activity and moderate increase in XO in patients with BD compared to controls indicating T cell activation and increased maturation. Serum AD activity of complete BD was higher than that of incomplete BD. There was no difference in XO activity between the subgroups of BD. Significant positive correlation was found between AD and XO in BD, although there was no correlation in control group.. The results indicate that increased AD and XO activities may provide an additional benefit for the diagnosis of BD and subtyping of the disease as having eye complication or not and complete and incomplete BD. Further studies are needed to bring to light the exact mechanism of AD and XO activity elevation.

Topics: Adenosine Deaminase; Adult; Behcet Syndrome; Case-Control Studies; Clinical Enzyme Tests; Eye Diseases; Female; Humans; Male; Middle Aged; Prospective Studies; Spectrum Analysis; T-Lymphocytes; Xanthine Oxidase