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Infection and Immunity, June 1999, p. 3047-3050, Vol. 67, No. 6
0019-9567/99/$04.00+0
Copyright © 1999, American Society for Microbiology. All rights reserved.

Interleukin-12 Enhances Antifungal Activity of Human Mononuclear Phagocytes against Aspergillus fumigatus: Implications for a Gamma Interferon-Independent Pathway

Emmanuel Roilides,^1,2 Sevasti Tsaparidou,¹ Isaac Kadiltsoglou,¹ Tin Sein,² and Thomas J. Walsh^2,*

Third Department of Pediatrics, University of Thessaloniki, and Hippokration Hospital, Thessaloniki GR-54642, Greece,¹ and Immunocompromised Host Section, Pediatric Oncology Branch, National Cancer Institute, Bethesda, Maryland 20892²

Received 25 August 1998/Returned for modification 2 October 1998/Accepted 22 March 1999

The potential of recombinant human interleukin-12 (IL-12) to enhance the capacity of human monocytes (MNC) to elicit an oxidative burst and damage hyphae of Aspergillus fumigatus was investigated. Incubation of peripheral blood mononuclear cells (PBMC) from healthy adults with 10 to 100 ng of IL-12/ml at 37°C for 2 to 3 days enhanced the production of superoxide anion (O₂) in response to phorbol myristate acetate (PMA) (P = 0.04) and unopsonized A. fumigatus hyphae (P = 0.03) and further enhanced hyphal damage (P = 0.009). Anti-gamma interferon (anti-IFN-) blocked secretion of IFN- by IL-12-treated PBMC but did not inhibit IL-12-induced O₂ production by these cells in response to PMA. In addition, IL-12-treated elutriated MNC secreted no IFN- or tumor necrosis factor alpha but exhibited enhanced O₂ production compared to controls (P = 0.013). These findings demonstrate that IL-12 augments oxidative antifungal activities of MNC via an IFN--independent route, suggesting a novel pathway of IL-12 action in antifungal defense.

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^* Corresponding author. Mailing address: Immunocompromised Host Section, Pediatric Oncology Branch, National Cancer Institute, Bldg. 10, Rm. 13N240, Bethesda, MD 20892. Phone: (301) 402-0023. Fax: (301) 402-0575. E-mail: walsht{at}exchange.nih.gov.

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Infection and Immunity, June 1999, p. 3047-3050, Vol. 67, No. 6
0019-9567/99/$04.00+0
Copyright © 1999, American Society for Microbiology. All rights reserved.

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