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IL-9 Protects Mice from Gram-Negative Bacterial Shock: Suppression of TNF-, IL-12, and IFN-, and Induction of IL-10

Ursula Grohmann^1,*, Jacques Van Snick, Franca Campanile^*, Silvia Silla^*, Antonio Giampietri^*, Carmine Vacca^*, Jean-Cristophe Renauld, Maria C. Fioretti^* and Paolo Puccetti^*

^* Department of Experimental Medicine, University of Perugia, Perugia, Italy; and Ludwig Institute for Cancer Research, Brussels, Belgium

IL-9 is a T cell-derived cytokine that, similar to the Th2 cytokines IL-4 and IL-10, has been implicated in the response to parasitic infections, allergy, and inflammatory processes. Because both IL-4 and IL-10 can confer protection to mice from septic shock, we investigated whether IL-9 may also be capable of conferring resistance on recipients of an otherwise lethal challenge with Pseudomonas aeruginosa. Prophylactic injections of rIL-9 appeared 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 protective effect of IL-9 was correlated with marked decreases in the production of the inflammatory mediators TNF-, IL-12, and IFN-, as well as the induction of the anti-inflammatory cytokine IL-10. 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 in septic shock via a rather unique mechanism involving a complex modulation of inflammatory and anti-inflammatory mediators.

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