PRODUCTION OF CYTOKINES BY ALVEOLAR AND PERITONEAL-MACROPHAGES STIMULATED BY ASPERGILLUS-FUMIGATUS CONIDIA OR HYPHAE

Aspergillus fumigatus is an opportunistic pathogen responsible for sev ere, invasive infections in neutropenic hosts. Lung clearance of A. fu migatus conidia seems to be mediated by phagocytic cells and oxygen ra dicals. It is not known if cytokines or nitrogen radicals are also inv olved. We tested for the production of TNF alpha, IL-1 and nitric oxid e (NO) after stimulation of mouse macrophages with the fungus. We foun d that both cytokines, but not NO, were produced in a dose-dependent m anner during the first 24 h of culture. Except for a faster kinetic, n o appreciable differences were seen between alveolar and peritoneal ma crophages. Furthermore, both hyphae and conidia, either alive or kille d, were capable of inducing cytokines production. However, among diffe rent Aspergillus spp. only A. fumigatus and A. flavus seemed to induce significant amount of TNF alpha and IL-1, whereas A. terreus and A. n iger were less effective. In no case could we detect production of NO. Finally, macrophages from dexamethasone-treated mice failed to produc e cytokines in response to A. fumigatus conidia. These results indicat e that in normal hosts inflammatory cytokines contribute to the natura l response against Aspergillus infections and suggest that the impairm ent of cytokine production, in immunodepressed patients, may favour th e growth and spread of the fungus.