Pharmacological characterisation of arthritis induced by Bothrops jararaca venom in rabbits: a positive cross talk between bradykinin, nitric oxide and prostaglandin E2.

BACKGROUND: Our previous results showed that nitric oxide (NO) and bradykinin (BK) mediate the arthritis induced by Bothrops jararaca venom (BjV) in rabbits. In this study, we investigated the contribution of each receptor of BK as well as the inter-relationship between NO and eicosanoids in BjV-induced arthritis. METHODS: The arthritis was induced in rabbits with 16 microg of BjV injected intra-articularly. Prostaglandin E2 (PGE2), thromboxane B2 (TxB2), leukotriene B4 (LTB4) (radioimmunoassay) and nitrite/nitrate concentrations (NO2/NO3) (Griess reaction) were evaluated in the synovial fluid 4 h later. The animals were prior treated with NO synthase inhibitor (L-NAME; 20 mg/kg/day for 14 days), the B2 antagonist of BK (HOE-140) and the B1 antagonist of BK (des-Arg9[Leu8]-bradykinin), both at a dose of 0.3mg/kg, 30 min prior to the venom injection. RESULTS: Data show that L-NAME and HOE-140 treatment were equally able to reduce PGE2 and NO2/NO3 levels without interfering with TxB2 and LTB4 production. On the contrary, the B1 antagonist of BK inhibited TxB2 and LTB4 production, and did not alter PGE2 and NO metabolites levels in the inflamed joint. DISCUSSIONS: The results presented clarify the contribution of the kinin system, mainly through the B2 receptor, to the local inflammatory response induced by BjV, as well as its positive interaction with PGE2 and NO production

Interleukin 18 as a marker of disease activity and severity in patients with juvenile idiopathic arthritis

Objective. To verify the importance of interleukin 18 (IL-18) in the pathogenesis of juvenile idiopathic arthritis (JIA). We measured IL-18 levels in synovial fluid (SF) and serum, and determined their correlation with measures of disease activity and severity.Methods. Fifty patients with JIA (13 systemic, 13 polyarticular, 24 oligoarticular) and 25 matched controls were analyzed. Cytokire levels (IL-1 beta, IL-1Ra, IL-6, and IL-18) were quantified in serum and SF by ELISA, and disease activity measures were evaluated immediately after knee articular puncture. Radiological assessment was made according to the Steinbrocker method. Statistical analysis was performed by Spearman's rank-order correlation and Mann-Whitney rank test.Results. All the analyzed cytokine levels (IL-1, IL-IRa, IL-6, and IL-18) were higher in patients' sera than in controls. Remarkably, in patients with JIA, IL-18 SF levels did not differ from those of serum; they were positively correlated. The levels of IL-18 (SF and serum) were positively correlated with measures of disease activity: C-reactive protein, number of active joints, and radiological score, as well as with levels of IL-1, IL-1Ra, and IL-6. Moreover, IL-18 and IL-6 levels in SF and serum were much higher in patients with systemic disease compared to the other types of disease onset. In contrast, IL-1 and IL-1Ra were not different among JIA subtypes.Conclusion. Our results strongly suggest the participation of IL-18 in the pathophysiology of JIA. The positive correlation of this cytokine with several measures of articular inflammation and disease severity suggests that IL-18 could be a better target for the treatment of arthritis.Univ Sao Paulo, Sch Med, Dept Internal Med, Div Rheumatol, BR-01246903 Sao Paulo, BrazilUniv Sao Paulo, Sch Med, Dept Pediat, BR-01246903 Sao Paulo, BrazilWeb of Scienc

In vivo blockade of Ca(+2)-dependent nitric oxide synthases impairs expressions of L-selectin and PECAM-1

Interactions of leukocytes with endothelium play a role for the immune system modulated by endogenous agents, such as glucocorticoids and nitric oxide (NO). Glucocorticoids inhibit leukocyte-endothelial interactions whereas the role of NO is still controversial. In this study, the activity of Ca(+2)-dependent nitric oxide synthases was in vivo blocked in male Wistar rats by given L-NAME, 20 mg kg(-1) for 14 days dissolved in drinking water and expression of adhesion molecules involved in leukocyte-endothelial interactions was investigated. Expressions of L-selectin and PECAM-I in peripheral leukocytes and PECAM-1 in endothelial cells were reduced by L-NAME treatment. Only L-selectin expression was controlled at transcriptional levels. These effects were not dependent on endogenous glucocorticoids, as corticosterone levels were not altered in NAME-treated rats. Our results show that NO, produced at physiological levels, controls expression of constitutive adhesion molecules expressions in cell membranes by different mechanisms of action. Published by Elsevier Inc.FAPESP[05/60329-0]Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES)CAPE