Exploring the relationship between oxidative stress status and inflammatory markers during primary Sjögren's syndrome: A new approach for patient monitoring.

INTRODUCTION: Primary Sjögren's syndrome (pSS) is a chronic inflammatory disease primarily affects exocrine glands dysfunction. Oxidative stress (OS) is a phenomenon occurring as a result of an imbalance between the generation of free radicals and antioxidant defense system. Hence, we aimed to establish the status of OS and inflammatory response according to the pSS disease activity index. In this context, we investigated malondialdehyde (MDA), and antioxidant enzymes during pSS. The possible association between MDA and nitric oxide (NO) levels and between MDA and some pro-inflammatory cytokines (IL-1ß, IL-6, TNF-α, and IL-33). METHODS: The study has been conducted on 53 pSS patients. The antioxidant enzymes, represented by glutathione peroxidase (GSH-Px), catalase (CAT) and superoxide dismutase (SOD), were estimated by a colorimetric activity kit. Whereas, MDA value was assessed by measuring thiobarbituric acid reactive substances. Moreover, pro-inflammatory cytokines (IL-1ß, IL-6, TNF-α, and IL-33) and NO were respectively quantified by enzyme-linked immunosorbent assays (ELISA) and the modified Griess. RESULTS: Interestingly, we report a notable reduction in our pSS patients' antioxidant enzyme activity, while NO, MDA and proinflammatory cytokines values were significantly increased. pSS patients with higher disease activity had much stronger increases in NO and MDA levels. No significant difference was assessed in CRP level. Additionally, substantial significant correlations between plasmatic NO and MDA levels and between MDA, NO and IL-1ß, IL-6, TNF-α cytokines were reported. However, no significant association was found between NO, MDA and IL-33 concentrations. CONCLUSION: Collectively, our data showed altered oxidant-antioxidant balance in pSS patients. MDA, NO, IL-1ß, IL-6, TNF-α seem to be good indicators in monitoring disease activity. Oxidative stress was closely related to inflammation in pSS. Exploiting this relationship might provide valuable indicators in the follow-up and prognosis of pSS with a potential therapeutic value.

Interferon-ß inhibits inflammatory responses mediators via suppression of iNOS signaling pathway in PBMCs from patients with primary Sjögren's syndrome.

BACKGROUND: Primary Sjögren's syndrome (pSS) represents a chronic, systemic autoimmune disorder, characterized by lymphocytic infiltration of exocrine glands, inducing compromised secretory function and tissue destruction. Increasing evidence had revealed that inflammatory mediators, such as nitric oxide (NO) and pro-inflammatory cytokines, are critical in the development and perpetuation of pSS systemic manifestations. In our current study, we aimed to investigate the ex vivo immunomodulatory effect of interferon (IFN)-ß on iNOS expression, as well as on pro-inflammatory (tumor necrosis factor (TNF)-α, interleukin (IL)-6) and immunoregulatory (IL-10) cytokine production. Furthermore, we examined potential associations between the influence of IFN-ß treatment on NO production, and pSS clinical and serological manifestations. METHODS: In 41 pSS patients documented for their clinical and serological features, NO and cytokines levels were measured by the Griess method and enzyme-linked immunosorbent assay, respectively. Inducible nitric oxide synthase expression was analyzed by fluorescence immunostaining assay, using peripheral blood mononuclear cells (PBMCs) isolated from healthy controls and pSS patients. RESULTS: Our results revealed a strong down-modulating effect of IFN-ß in the secretion of pro-inflammatory mediators including TNF-α, IL-6, and NO production. Interestingly, IFN-ß exerts an increase in IL-10 levels. The most suppressive effect exerted by IFN-ß on NO production was importantly reported for patients with neurological manifestation. This immunomodulatory effect of IFN-ß on NO production is highly related to the decrease of inducible nitric oxide synthase (iNOS) expression. CONCLUSION: Our findings highlight a consistent ex vivo inhibitory effect of IFN-ß on pro-inflammatory cytokine production and NO pathway in pSS patients. Our data suggest that IFN-ß could represent a potential candidate for targeting inflammation during pSS.