Interleukin-12 enhances antifungal activity of human mononuclear phagocytes against Aspergillus fumigatus: Implications for a gamma interferon-independent pathway

The potential of recombinant human interleukin-12 (IL-12) to enhance the ca pacity of human monocytes (MNC) to elicit an oxidative burst and damage hyp hae of Aspergillus:fumigatus was investigated. Incubation of peripheral blo od mononuclear cells (PBMC) from healthy adults with 10 to 100 ng of IL-12/ ml at 37 degrees C for 2 to 3 days enhanced the production of superoxide an ion (O-2(-)) in response to phorbol myristate acetate (PMA) (P = 0.04) and unopsonized A. fumigatus hyphae (P = 0.03) and further enhanced hyphal dama ge (P = 0.009). Anti-gamma interferon (anti-IFN-gamma) blocked secretion of IFN-gamma by IL-12-treated PBMC but did not inhibit IL-12-induced O-2(-) p roduction by these cells in response to PMA. In addition, IL-12-treated elu triated MNC secreted no IFN-gamma or tumor necrosis factor alpha but exhibi ted enhanced O-2(-),- production compared to controls (P = 0.013). These fi ndings demonstrate that IL-12 augments oxidative antifungal activities of M NC via an IFN-gamma-independent route, suggesting a novel pathway of IL-12 action in antifungal defense.