Protection against Lipopolysaccharide-induced Death by An Anti-Interleukin-6 Monoclonal Antibody

Abstract

Septicemia is frequently associated with serious complications and high mortality despite recent advances in treatment with antibacterial agents. Infectious organisms or their soluble products initiate septic shock through a complex cytokine cascade. Lipopolysaccharide (LPS) induced excessive production of inflammatory cytokines is regarded as a model of septic shock. Experiments of LPS-induced excessive cytokine production were conducted in Balb/c mice for the investigation of the therapeutic potential of anti-TNF-α and anti-IL-6 monoclonal antibody treatments. LPS injection resulted in mortality with significant serum levels of TNF-α, IL-6, and IL-1β. Anti-IL-6 treatment significantly reduced animal mortality and inhibited serum levels of IL-6. Anti-TNF-α treatment did not affect serum IL-6 levels even though it significantly enhanced animal survival and inhibited TNF-α production. Moreover, anti-IL-6 treatment modestly reduced serum TNF-α level in comparison with control antibody treated group. These data suggest that TNF-α and IL-6 may play distinct protective roles in septic shock.