TUMOR NECROSIS FACTOR RECEPTOR 1 (TNFR1) NEUTRALIZATION AMELIORATED CARRAGEENAN-INDUCED INFLAMMATION IN MICE SUPPLEMENTED WITH HERBAL ANTIOXIDANTS

TNF-α plays pivotal role in initiation of inflammation via its interaction with TNFR1 in an O₂^.- induced oxidative stress dependent manner. The present study investigated whether the anti-oxidant effect of hydroalcoholic extract of Clitoria ternatea (CTE), could facilitate the anti-inflammatory effect of TNFR1 neutralization in context to carrageenan-induced acute inflammation in mice. Sub-plantar injection of λ-carrageenan (0.1% in saline) elicited profound inflammatory reactions in plantar tissue 0-12 hour (h) post carrageenan injection (p.c.i.), as evident from increased PMN infiltration (myeloperoxidase activity), local and systemic release of cytokines and chemokines, free radical generation and oxidative stress in male Swiss albino mice (20 – 22g, 3 – 4 weeks of age). The inflammatory reactions were attenuated from 6 – 12 h pci in CTE (50 mg/kg) and QG (2.5 mg/kg) pre-treated mice, and were potentiated followed by TNFR1 neutralization with anti-TNFR1 antibody (10 μg/mouse) in terms of significant decreases (p < 0.05) in PMN infiltration, pro-inflammatory cytokines and chemokines as well as ROS/RNS generation and oxidative stress in parallel to decreased TNFR1 and NF-κB mediated COX-2 and iNOS expression from 4 – 12 h pci. Results suggested that anti-inflammatory effect exerted by CTE or QG were potentiated following antibody mediated TNFR1 neutralization which might become a reliable combinatorial approach to combat inflammatory diseases in future therapeutic research.