Exogenous IL ‐10 post‐treatment along with TLR4 and TNFR1 blockade improves tissue antioxidant status by modulating sepsis induced macrophage polarization

AbstractMulti-organ dysfunction is one of the major reasons behind the high mortality of sepsis throughout the world. With the pathophysiology of sepsis remaining largely unknown, the uncontrolled ROS production along with the decreased anti-oxidants contributes to the progression toward septic shock. Being the effector cells of the innate immunity system, macrophages secrete both pro- as well as anti-inflammatory mediators during inflammation. LPS binding to TLR4 releases TNF- α which initiates pro-inflammatory events through TNFR1 signaling. However, it is counteracted by the anti-inflammatory IL-10 causing decreased oxidative stress. Our study thus aimed to assess the effects of exogenous IL-10 treatment post-neutralization of TLR4 and TNFR1 (by anti-TLR4 antibody and anti-TNFR1 antibody respectively) in an in-vivo murine model of LPS-sepsis. We have also examined the tissue-specific antioxidant status in the spleen, liver, and lungs along with the serum cytokine levels in adult male Swiss albino mice to determine the functional association with the disease. The results showed that administration of recombinant IL-10 post-neutralization of the receptors was beneficial in shifting the macrophage polarization to the anti-inflammatory M2 phenotype. IL-10 treatment significantly down-regulated the free radicals production resulting in diminished LPO levels. The increased antioxidant activities of SOD, CAT, and GRX conferred protection against LPS induced sepsis. Western blot ...
Source: Journal of Applied Toxicology - Category: Toxicology Authors: Tags: RESEARCH ARTICLE Source Type: research