M Gharaee-Kermani and SH Phan
Department of Pathology, University of Michigan Medical School, Ann Arbor 48109-0602, USA.

Eosinophils are primary sources of fibrogenic cytokines in lung fibrosis, and interleukin (IL)-5 is important in their differentiation, proliferation, recruitment and activation. To investigate the potential role of this cytokine, lung IL-5 expression was examined in a murine model of bleomycin-induced pulmonary fibrosis. Analysis of lung RNA showed significant increases in lung IL-5 mRNA content between days 3 and 14 after induction of lung injury, which decreased toward control levels after day 21. In situ hybridization revealed essentially no detectable IL-5 mRNA expression before day 3, but showed elevated expression in mononuclear cells and eosinophils between days 3 and 14, localized within areas of active fibrosis. After 21 days, the intensity and number of IL-5-expressing cells significantly declined. Immunostaining with anti-IL-5 antibodies confirmed the predominant IL-5 expression by mononuclear cells and eosinophils in areas of active fibrosis. The kinetics of increase in the number of cells expressing significant IL-5 mRNA in lung sections paralleled that for IL-5 mRNA expression in whole-lung homogenates. These results demonstrate for the first time that IL-5 is upregulated in this murine model and suggest a novel role for this cytokine in pulmonary fibrosis via its ability to recruit and activate eosinophils.

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