Impaired interleukin 12 production in human immunodeficiency virus- infected patients

doi:10.1084/jem.179.4.1361

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Impaired interleukin 12 production in human immunodeficiency virus- infected patients

J Chehimi, SE Starr, I Frank, A D'Andrea, X Ma, RR MacGregor, J Sennelier and G Trinchieri
Division of Allergy, Immunology and Infectious Diseases, Children's Hospital of Philadelphia, Pennsylvania.

Peripheral blood mononuclear cells (PBMC) from human immunodeficiency virus (HIV)-infected patients, asymptomatic or with acquired immunodeficiency virus, produced 10-fold less interleukin 12 (IL-12) free heavy chain and fivefold less biologically active IL-12 heterodimer than PBMC from uninfected healthy donors when challenged in vitro with the common human pathogen Staphylococcus aureus. In contrast, PBMC from HIV-infected individuals and uninfected control donors produced similar levels of tumor necrosis factor alpha, IL-1 beta, and IL-10, and PBMC from HIV-infected individuals produced three- to fourfold more IL-6 compared with PBMC from uninfected control donors. The defect in IL-12 production is not due to hyperproduction of IL-10, a cytokine exerting an autocrine-negative feedback on IL-12 production, but was directly related to HIV infection, as suggested by the reduced ability of monocytes infected in vitro with HIV to produce IL-12. IL-12 deficiency may be an important component of the immunodeficiency associated with HIV infection.
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