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

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.