ROLE OF IL-12 IN PERIPHERAL-BLOOD MONONUCLEAR CELL RESPONSES TO FUNGIIN PERSONS WITH AND WITHOUT HIV-INFECTION

Clinical trials of IL-12 in persons infected with HIV have been propos ed based on recent evidence suggesting IL-12 plays a critical role in the development of protective immune responses, and that HIV infection is associated with a deficiency of IL-12. As fungal infections are am ong the most common opportunistic infections associated with AIDS, we examined whether IL-12 p40 gene expression and p70 release in response to Cryptococcus neoformans and Candida albicans were deficient in mon ocyte-enriched PBMC from HIV-seropositive donors and whether rIL-12 co uld augment the proliferation of PBMC from HIV-seropositive donors in response to these fungi and to Pneumocystis carinii. PBMC from HIV-ser onegative donors expressed IL-12 p40 mRNA in response to C. neoformans , C. albicans, and the positive control Staphylococcus aureus Cowan st rain 1 (SAC), although the induction of IL-12 p40 mRNA was later acid more prolonged with C. neoformans as the stimulus. Expression of IL-12 p40 mRNA in response to the three stimuli was similar in cells from H IV-seropositive and HIV-seronegative donors. However, when stimulated with SAG, cells from HIV-seropositive donors released significantly le ss IL-12, suggesting HIV infection induces a post-transcriptional defe ct in IL-12 release in response to SAG. While PBMC from HIV-seropositi ve donors had impaired proliferative responses to the three fungi test ed, addition of rIL-12 did not enhance proliferation. These studies do not lend further support for the therapeutic use of IL-12 to prevent or treat Fungal infections in persons infected with HIV.