INTERLEUKIN-6 IS REQUIRED FOR A PROTECTIVE IMMUNE-RESPONSE TO SYSTEMIC ESCHERICHIA-COLI INFECTION

Interleukin-6 (IL-6) is a multipotential cytokine detected in the seru m of patients or experimental animals undergoing bacterial sepsis. To date, the role of IL-6 in gram-negative sepsis models has been controv ersial, We have used IL-6-deficient mice to investigate the role of IL -6 during virulent Escherichia coli infection and in lipopolysaccharid e (LPS)-induced mortality. In this report we describe an increased sus ceptibility of IL-6-deficient mice to E. coli infection in terms of mo rtality and accumulation of viable bacteria in tissues, indicating a p rotective role for IL-6 during the immune response against E. coli. In contrast, mortality rates of IL-6-deficient mice and control animals undergoing LPS-induced shock did not differ, indicating that IL-6 was inconsequential for survival in this model. Furthermore, we have shown that neutrophils were crucial for resistance to E. coli in normal mic e, IL-6-deficient mice were unable to efficiently induce neutrophilia in the bloodstream immediately following challenge with E. coli, in co ntrast to a characteristic neutrophilia induced in control animals. Pr ophylactic treatment of the mutant animals with recombinant IL-6 prote in reverted both the deficit of neutrophilia and the accumulation of b acteria in tissues. These data clarify the role of IL-6 as protective in virulent E. coli infection and suggest that the protective effect m ay be at least partially mediated through neutrophils.