KINETIC-STUDY OF HOST-DEFENSE AND INFLAMMATORY RESPONSE TO ASPERGILLUS-FUMIGATUS IN STEROID-INDUCED IMMUNOSUPPRESSED MICE

The sequential pathogenesis of pulmonary aspergillosis was studied and the role of inflammatory cytokines in host response to Aspergillus fu migatus was characterized in immunocompetent and immunosuppressed mice . Two distinct phases were observed in immunocompetent mice: First, an intense clearance of A. fumigatus occurred, possibly through alveolar macrophages and recruited neutrophils (PMNL), accompanied by rapid re lease of tumor necrosis factor-alpha, interleukin (IL)-6, and IL-1 bet a, and second, cellular and fungal debris were cleaned by recruited mo nocytes, cytokine production rapidly decreased, and pneumonia self-hea led. In contrast, cortisone-treated animals had, first, an altered cle arance of conidia and delayed cytokine production and inflammatory cel l recruitment; second, an invasive process in lungs, recruitment of PM NL, and release of IL-6 and IL-1 beta; and third, widespread tissue ne crosis, sustained release of IL-6 and IL-1 beta, further increases in PMNL trafficking but no monocyte recruitment, respiratory failure, and 100% mortality within 5 days. These insights may be useful in the dev elopment of new treatment strategies for pulmonary aspergillosis.