Interleukin 9 promotes influx and local maturation of eosinophils

The interleukin 9 (IL-9) pathway has recently been associated with the asth matic phenotype including an eosinophilic tissue inflammation. The mechanis m by which IL-9 affects eosinophils (eos) is not known. To investigate whet her this cytokine has a direct activity on the development of eos and eosin ophilic inflammation, a model of thioglycolate-induced peritoneal inflammat ion was used in IL-9 transgenic (TG5) and back ground strain (RIB) mice. In this model, a transient eosinophilic infiltration in the peritoneal cavity was observed in FVB mice 12 to 24 hours after thioglycolate injection that coincided with peak IL-5 and IL-9 release. In contrast, TG5 mice developed a massive eosinophilia that persisted at high levels (81% of total cells) even 72 hours after thioglycolate injection. Release of eosinophilic major basic protein (MBP), IL-4, and IL-5 to the peritoneal cavity of these mice was significantly increased when compared with the control RIB strain. To s tudy the mechanism by which IL-9 exerts its effect on eos, bone marrow or p eritoneal cells were cultured in the presence of IL-5, IL-9, or their combi nation in vitro. IL-5 alone was able to generate significant numbers of eos in TG5 but not FVB mice, whereas a combination of IL-5 and IL-9 induced ma rked eosinophilia in both strains indicating a synergism between these 2 cy tokines, These data suggest that IL-9 may promote and sustain eosinophilic inflammation via IL-5-driven eos maturation of precursors. (C) 2001 by The American Society of Hematology.