Am. J. Respir. Cell Mol. Biol., Volume 26, Number 4, April, 2002 404-412

Interleukin-15 Inhibits Spontaneous Apoptosis in Human Eosinophils via Autocrine Production of Granulocyte Macrophage-Colony Stimulating Factor and Nuclear Factor-B Activation

Raweewan Hoontrakoon, Hong Wei Chu, Shyra J. Gardai, Sally E. Wenzel, Patrick McDonald, Valerie A. Fadok, Peter M. Henson, and Donna L. Bratton

Department of Pediatrics, Division of Allergy and Immunology and Department of Medicine, Division of Pulmonology, National Jewish Medical and Research Center, Denver, Colorado; and Centre De Recherche Clinique Sherbrooke, Quebec, Canada

Prolonged eosinophil survival, i.e., reduced apoptosis, is implicated in the pathogenesis of chronic allergic inflammation. Here we demonstrate that interleukin (IL)-15, in the presence or absence of tumor necrosis factor (TNF)-, reduces spontaneous apoptosis in freshly isolated human eosinophils. The prosurvival effect of IL-15 was abrogated by neutralizing antibody to granulocyte macrophage-colony stimulating factor (GM-CSF), although GM-CSF was not detected in conditioned media by ELISA. Additionally, the effect of IL-15 on spontaneous eosinophil apoptosis appeared to require nuclear factor-B (NF-B) activation based on evidence for NF-B nuclear translocation and abrogation of the effect by the NF-B inhibitor, Bay 11- 7082. Finally, the data demonstrate that IL-15 expression is higher in the submucosa of endobronchial tissues from subjects with moderate to severe asthma when compared with control subjects. Thus, our results suggest that IL-15, either alone or in combination with TNF-, may perpetuate allergic inflammation by reduction of spontaneous eosinophil apoptosis through autocrine production of GM-CSF and NF-B activation.

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