Tumor necrosis factor alpha enhances antifungal activities of polymorphonuclear and mononuclear phagocytes against Aspergillus fumigatus

Invasive aspergillosis is a serious complication in immunocompromised patie nts. The effects of recombinant human tumor necrosis factor alpha (TNF-alph a) on antifungal activities of human neutrophils (polymorphonuclear leukocy tes [PMNs]), human monocytes (MNCs), and rabbit pulmonary alveolar macropha ges (PAMs) against Aspergillus fumigatus were studied. The percentage of PM N-induced hyphal damage was increased after 30 min of incubation of PMNs wi th 0.1 ng of TNF-alpha per ml at 37 degrees C (P = 0.043). At 0.1 to 10 ng/ ml, TNF-alpha also increased superoxide anion (O-2(-)) produced by PMNs in response to phorbol myristate acetate, N-formylmethionyl leucyl phenylalani ne, and unopsonized hyphae (P < 0.01) but did not exert any effect on PMN p hagocytosis of conidia in the presence of serum, By comparison, TNF-alpha i nduced only a slight increase in O-2(-) production by MNCs in response to p horbol myristate acetate (P = 0.05) and no concomitant increase in the perc entage of MNC-induced hyphal damage. Incubation of MNCs with TNF-alpha at 0 .001 to 10 ng/ml for 2 days had no effect on phagocytosis or conidiocidal a ctivity. By contrast, incubation of PAMs with TNF-alpha at 0.1 to 10 ng/ml for 2 days increased phagocytosis of conidia (P = 0.03). Thus, TNF-alpha au gments the capacity of PMNs to damage Aspergillus hyphae, possibly through enhanced oxidative mechanisms, and increases PAM phagocytic activity agains t conidia. As such, TNF-alpha may have an important role in host defense ag ainst aspergillosis, and neutralization of its activity may be complicated by increased susceptibility to aspergillosis.