Impaired interleukin 12 production in human immunodeficiency virus-infected patients.
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.
Chehimi
J
J
Division of Allergy, Immunology and Infectious Diseases, Children's Hospital of Philadelphia, Pennsylvania.
Starr
S E
SE
Frank
I
I
D'Andrea
A
A
Ma
X
X
MacGregor
R R
RR
Sennelier
J
J
Trinchieri
G
G
D000328:Adult; D002460:Cell Line; D005260:Female; D015658:HIV Infections / Q000276:immunology*; D006801:Humans; D018664:Interleukin-12; D007378:Interleukins / Q000096:biosynthesis*; D008297:Male; D008875:Middle Aged; D009000:Monocytes / Q000378:metabolism; D013211:Staphylococcus aureus / Q000276:immunology
D007378:Interleukins; D018664:Interleukin-12