IL-9 protects mice from gram-negative bacterial shock: Suppression of TNF-alpha, IL-12, and IFN-gamma, and induction of IL-10

IL-9 is a T cell derived cytokine that, similar to the Th2 cytokines IL-4 a nd IL-10, has been implicated in the response to parasitic infections, alle rgy, and inflammatory processes. Because both IL-4 and IL-10 can confer pro tection to mice from septic shock, we investigated whether IL-9 may also be capable of conferring resistance on recipients of an otherwise lethal chal lenge with Pseudomonas aeruginosa. Prophylactic injections of rIL-9 appeare d to be most effective in preventing the onset of a lethal shock, according to a pattern that was both dose dependent and time dependent. The protecti ve effect of IL-9 was correlated with marked decreases in the production of the inflammatory mediators TNF-alpha, IL-12, and IFN-gamma, as well as the induction of the anti-inflammatory cytokine LL-IO, Sustained levels of IL- 9-specific transcripts could be detected in the spleens of mice recovering from sublethal P. aeruginosa infection. Therefore, IL-9 may be protective i n septic shock via a rather unique mechanism involving a complex modulation of inflammatory and anti-inflammatory mediators.