Protective effects of interleukin-6 in lipopolysaccharide (LPS)-induced experimental endotoxemia are linked to alteration in hepatic anti-oxidant enzymes and endogenous cytokines

Abstract

Endogenous interleukin-6 has been considered as an important anti-inflammatory cytokine controlling both local and systemic acute inflammatory responses; the usefulness of IL-6 in endotoxemia aiming to block the production of reactive oxygen species and the release of inflammatory cytokines is under discussion The aim of the study was to evaluate the protective effects of IL-6 in experimentally induced endotoxemia in mice correlating the changes in tissue anti-oxidant enzymes and circulating cytokines. Liver injury in low-dose bacterial lipopolysaccharide (5 μg/mouse)-induced endotoxemic mice receiving IL-6 (300 ng/mouse) treatment either before or after LPS injection was detected by the estimation of serum oxaloacetate transaminase and serum glutamate pyruvate transaminase. This finding supports that liver injury during experimental endotoxemia could be lowered by IL-6. Current data also demonstrate the critical role of IL-6 in inducing SOD in liver, whereas IL-6 prior and after LPS challenge group showed reduced PMN infiltration in the liver as evident by decreased hepatic MPO content in those mice. IL-6 treatment also showed higher IL-10 production in serum than endotoxic group as IL-10 is a potent and pleiotropic anti-inflammatory cytokine that inhibits the synthesis of pro-inflammatory cytokines and also has a suppressive effect on pro-inflammatory cytokine like TNF-α, IFN-γ and IL-12. It is also directly involved in the modulation of other aspects of inflammation, particularly cytokine responses and inflammatory cell infiltration.