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 serum of patients or experimental animals undergoing bacterial sepsis. To date, the role of IL-6 in gram-negative sepsis models has been controversial. We have used IL-6-deficient mice to investigate the role of IL-6 during virulent Escherichia coli infection and in lipopolysaccharide (LPS)-induced mortality. In this report we describe an increased susceptibility of IL-6-deficient mice to E. coli infection in terms of mortality and accumulation of viable bacteria in tissues, indicating a protective 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 mice. IL-6-deficient mice were unable to efficiently induce neutrophilia in the bloodstream immediately following challenge with E. coli, in contrast to a characteristic neutrophilia induced in control animals. Prophylactic treatment of the mutant animals with recombinant IL-6 protein reverted both the deficit of neutrophilia and the accumulation of bacteria in tissues. These data clarify the role of IL-6 as protective in virulent E. coli infection and suggest that the protective effect may be at least partially mediated through neutrophils.
Dalrymple
S A
SA
Department of Immunology, DNAX Research Institute, Palo Alto, Calfiornia 94304, USA.
Slattery
R
R
Aud
D M
DM
Krishna
M
M
Lucian
L A
LA
Murray
R
R
D000818:Animals; D004926:Escherichia coli / Q000254:growth & development / Q000472:pathogenicity; D004927:Escherichia coli Infections / Q000276:immunology* / Q000401:mortality; D007113:Immunity, Innate; D015850:Interleukin-6 / Q000172:deficiency / Q000235:genetics / Q000276:immunology* / Q000494:pharmacology; D008099:Liver / Q000382:microbiology; D051379:Mice; D008817:Mice, Mutant Strains; D009504:Neutrophils / Q000276:immunology; D011994:Recombinant Proteins / Q000494:pharmacology; D012772:Shock, Septic / Q000276:immunology* / Q000401:mortality; D013154:Spleen / Q000382:microbiology; D016019:Survival Analysis; D014774:Virulence
D015850:Interleukin-6; D011994:Recombinant Proteins