Increased Salivary Cytokines and Nitric Oxide Levels in Behçet's Disease: Interleukin-32, a Novel Player in Disease Prognosis.

BACKGROUND: Oral aphthosis is one of the major manifestations of Behçet's disease (BD), a chronic, multisystemic vasculitis. BD etio-pathogenicity related to oral health lack. OBJECTIVE: This study investigated the possible relationships between poor oral hygiene, oral activity, disease severity and saliva's Interleukin (IL)-32, IL-6, IL-10 and nitric oxide (NO) levels in Behçet's patients to determine their role in disease prognosis and their potential therapeutic interest. METHODS: Fifty-six patients with BD (22 orally active; 34 orally inactive) and 31 healthy subjects have been included in our study. Salivary levels of IL-32, IL-6, and IL-10 were measured using ELISA, while NO levels were assessed by modified Griess's method. Oral health status and disease severity scores were recorded for each participant. Kruskal-Wallis test and Spearman's test were performed for statistical analyses. RESULTS: We observed that the tested molecules were increased in BD patients compared to healthy controls (p˂0.05). Moreover, only IL-32 levels were associated with oral activity in patients (p˂0.05). Interestingly, the disease severity score was noted to be correlated positively and significantly with both IL-32 saliva levels (p˂0.01) and plaque index (p˂0.05) in BD patients. Furthermore, IL-32 levels were correlated with plaque index (p˂0.0001). CONCLUSION: Our results suggest that IL-32, IL- 6, IL-10 and NO were increased in saliva during BD. Our study indicated that IL-32 was associated with the genesis of oral ulcers in response to dental plaque. Ultimately, salivary IL-32 may serve as a prognostic biomarker and a possible therapeutic target for managing Behçet's disease severity.

In-vitro immunomodulatory effects of nicotine on Nitric Oxide, interleukin 1ß and interleukin 37 production in human peripheral blood mononuclear cells (PBMC) from patients with Behçet disease.

Behçet's disease is a chronic systemic inflammatory disorder associated with a cytokine profile disruption and increased nitric oxide levels. In our current study we sought to evaluate the in-vitro modulatory effect of nicotine, the principal alkaloid of tobacco, on nitric oxide (NO), interleukin 1ß (IL-1ß) and interleukin 37 (IL-37) production during Behçet's disease. Peripheral blood mononuclear cells cultures were performed with or without nicotine (200 µg/ml). Culture supernatants were harvested after 24 h of incubation. NO, IL-1ß and IL-37 measurements were, respectively, performed by modified Griess method and ELISA sandwich. Our results showed that nicotine significantly reduced NO and IL-1ß levels in patients with Behçet's disease, while it increased IL-37 production. Our results showed no sex differences in the effects of nicotine on the production of nitric oxide and IL-1ß nor IL-37 in PBMC of patients. Our findings suggest that nicotine may provide a potential therapeutic strategy targeting inflammation during Behçet's disease.

Uric acid increases IL-1ß secretion and Caspase-1 activation in PBMCs of Behçet's disease patients: The in vitro immunomodulatory effect of xanthine oxidase inhibitor Allopurinol.

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-1ß/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-1ß 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-1ß 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-1ß, and Caspase-1 activity levels in PBMCs of BD patients, Allopurinol has exerted an immunomodulatory effect resulting in reduced NO, IL-1ß 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.

Management Of Glaucoma In Developing Countries: Challenges And Opportunities For Improvement.

Glaucoma is the leading cause of blindness in the developed and developing world. Not only is the clinical impact of this disease considerable, but associated economic and humanistic burdens - affecting patients, caregivers, and society - are substantial. Since glaucoma is an age-related disorder and populations in many developing countries are aging at a faster pace than in the developed world, increasing attention is being focused on ways to ameliorate the burdens of illness. In this paper, we examine the burdens of glaucoma with particular focus on developing countries, discuss some of the challenges that exist in delivering optimal glaucoma management within budget constraints, and bring into perspective how we could improve current healthcare systems, leverage technology, and strike an appropriate balance between cost and quality of care, thereby offering considerations to payors and policymakers in these countries that may result in longer-term cost savings, while concurrently striving to achieve the WHO Vision on the prevention of blindness and visual impairment.

Increased IL-1ß levels are associated with an imbalance of "oxidant/antioxidant" status during Behçet's disease.

Behçet's disease is a multisystem disease. It stands at the crossroad between the autoimmunity and auto-inflammatory disorders. In this study, we sought to address a relationship that might exist between interleukin-1ß (IL-1ß) and the oxidants/antioxidants markers in Behçet's patients. Behçet's disease patients (n = 78: active stage, n = 28; inactive stage, n = 50) and 41 healthy controls have been included in our study. In this context, we investigated the plasma levels of IL-1ß and the nitrosative/oxidative markers: nitric oxide (NO), advanced oxidative protein products (AOPP) and fatty acids peroxidation-malondialdehyde (MDA). The antioxidant system was assessed by measuring the plasma level of superoxide dismutase (SOD) activity. The Mann-Whitney's U and Pearson's correlation tests were used for statistical analyses. Our case-control study showed that patients in active stage displayed higher plasma levels of IL-1ß, NO, AOPP and MDA versus healthy controls and patients in inactive stage. Patients in active stage showed significantly lower SOD levels related to patients in inactive stage and healthy controls respectively, whereas patients in inactive stage showed statistically insignificant SOD level versus healthy controls. Correlation studies showed a significant positive correlation between IL-1ß and AOPP, IL-1ß and NO, and negative correlation between IL-1ß and SOD among Behçet's disease patients. In addition, we showed positive correlation between AOPP and NO, AOPP and MDA and negative correlation between NO and SOD, AOPP and SOD in Behçet's disease patients. Interestingly, our study revealed that IL-1ß levels increased and correlated with an imbalance of oxidants/antioxidants system, especially during active stage of Behçet disease. Collectively, our study indicates a possible link between IL-1ß production and nitrosative/oxidative markers during Behçet's disease. Exploiting this relationship might provide valuable outputs in the follow-up and prognosis of Behçet's disease with a potential therapeutic value.

Ex vivo effects of flavonoïds extracted from Artemisia herba alba on cytokines and nitric oxide production in Algerian patients with Adamantiades-Behçet's disease.

BACKGROUND: Adamantiades-Behçet's disease (ABD) is a chronic multisystemic inflammation with unknown pathophysiology. This disorder is associated with a dysregulation of the cytokine network that hyperactivates neutrophils and macrophages. In this study, we investigate the modulatory effects of flavonoïd compounds extracted from Algerian medicinal plant Artemisia herba alba on Th1 and Th2 cytokines and nitric oxide production. METHODS: The modulatory effects of flavonoïds extracted from Artemisia herba alba on cytokines and nitric oxide production by peripheral blood mononuclear cells isolated from Algerian ABD patients and healthy controls were respectively measured by means of ELISA assays and Griess modified method. RESULTS: Our results show that flavonoïds significantly reduce the production of interleukin-12, the key effector of T helper 1 (Th1) cells and nitric oxide in a dose-dependent manner in Adamantiades-Behçet's disease. In contrast, the production of IL-4, the key marker of Th2 cells was increased. CONCLUSION: This study suggests that in vitro supplementation with flavonoïds extracted from Artemisia herba alba could have potential immuno-modulatory effects characterised by a down-regulation and up-regulation of Th1 and Th2 cytokines, respectively. Moreover, flavonoïds may prevent nitric oxide induced damages.