Role of IL-12 in peripheral blood mononuclear cell responses to fungi in persons with and without HIV infection.
Clinical trials of IL-12 in persons infected with HIV have been proposed based on recent evidence suggesting IL-12 plays a critical role in the development of protective immune responses, and the HIV infection is associated with a deficiency of IL-12. As fungal infections are among 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 monocyte-enriched PBMC from HIV-seropositive donors and whether rIL-12 could augment the proliferation of PBMC from HIV-seropositive donors in response to these fungi and to Pneumocystis carinii. PBMC from HIV-seronegative donors expressed IL-12 p40 mRNA in response to C. neoformans, C. albicans, and the positive control Staphylococcus aureus Cowan strain 1 (SAC), although the induction of IL-12 p40 mRNA was later and 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 HIV-seropositive and HIV-seronegative donors. However, when stimulated with SAC, cells from HIV-seropositive donors released significantly less IL-12, suggesting HIV infection induces a post-transcriptional defect in IL-12 release in response to SAC. While PBMC from HIV-seropositive donors had impaired proliferative responses to the three fungi tested, 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.
Harrison
T S
TS
The Evans Memorial Department of Clinical Research and Department of Medicine, Boston University Medical Center Hospital, MA 02118
Levitz
S M
SM
D017088:AIDS-Related Opportunistic Infections / Q000150:complications / Q000517:prevention & control / Q000628:therapy; D001483:Base Sequence; D002176:Candida albicans / Q000276:immunology; D003455:Cryptococcus neoformans / Q000276:immunology; D017931:DNA Primers / Q000235:genetics; D005658:Fungi / Q000276:immunology*; D015658:HIV Infections / Q000276:immunology* / Q000628:therapy; D018023:HIV Seronegativity / Q000276:immunology; D006679:HIV Seropositivity / Q000276:immunology; D006801:Humans; D007167:Immunotherapy; D066298:In Vitro Techniques; D018664:Interleukin-12 / Q000097:blood* / Q000235:genetics / Q000494:pharmacology*; D007963:Leukocytes, Mononuclear / Q000276:immunology*; D008213:Lymphocyte Activation; D008969:Molecular Sequence Data; D009181:Mycoses / Q000150:complications / Q000517:prevention & control / Q000628:therapy; D016133:Polymerase Chain Reaction; D011994:Recombinant Proteins / Q000235:genetics / Q000494:pharmacology
D017931:DNA Primers; D011994:Recombinant Proteins; D018664:Interleukin-12