Endogenous interleukin-12 improves the early antimicrobial host response to murine Escherichia coli peritonitis.
Interleukin (IL)-12 is a heterodimeric proinflammatory cytokine formed by a p35 and a p40 subunit. To determine the role of IL-12 in abdominal sepsis, p35 gene-deficient (IL-12 knockout, KO) mice and normal wild-type (WT) mice were injected intraperitoneally with Escherichia coli. Peritonitis was associated with a bacterial dose-dependent increase in IL-12 p40 and IL-12 p75 concentrations in peritoneal fluid and plasma. Whereas at 6 h postinfection, IL-12 KO and WT mice displayed similar bacterial counts, at 20 hours IL-12 KO mice had significantly more bacteria in liver homogenates and were more susceptible to progressing to systemic infection. In addition, IL-12 KO mice demonstrated higher levels of proinflammatory cytokines in peritoneal fluid and increased lung and liver injury. IL-12 deficiency did not influence the recruitment of cells to the site of the infection. These data suggest that endogenous IL-12 is involved in the early antibacterial host response during abdominal sepsis.
Weijer
Sebastiaan
S
Laboratory of Experimental Internal Medicine, Tropical Medicine & AIDS, and University of Amsterdam, Amsterdam, The Netherlands.
Florquin
Sandrine
S
van der Poll
Tom
T
D000818:Animals; D016207:Cytokines / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D004926:Escherichia coli / Q000378:metabolism*; D004927:Escherichia coli Infections / Q000378:metabolism / Q000628:therapy*; D007249:Inflammation; D018664:Interleukin-12 / Q000235:genetics* / Q000378:metabolism / Q000502:physiology*; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D010538:Peritonitis / Q000378:metabolism / Q000628:therapy*; D018805:Sepsis; D013997:Time Factors
D016207:Cytokines; D018664:Interleukin-12