Induction of interleukin-6 during human immunodeficiency virus infection.
Interleukin-6 (IL-6), a multifunctional cytokine produced in monocytes, fibroblasts, and other cell types, is induced by a variety of stimuli, including bacteria, viruses, and other cytokines. When normal monocyte cultures were exposed to a monocytotropic strain of human immunodeficiency virus (HIV), HTLV-IIIBa-L, significant levels of IL-6 bioactivity were detected in the culture supernatants after 12 to 43 days of incubation, at a time when there was associated evidence of HIV production. Similarly, when normal monocyte cultures were cocultured with peripheral blood mononuclear cells from HIV-infected individuals, HIV replication in these cultures was associated with production of IL-6. In further studies, we determined that mean serum levels of IL-6 bioactivity were abnormally elevated in HIV-seropositive individuals with stage 1/2 infection (25.2 x/divided by 1.8 U/mL) and stage 3/4 infection (46.1 x/divided by 1.7 U/mL) when compared with normals (1.6 x/divided by 1.2 U/mL). In contrast mean serum IL-6 levels were not different from normal in stage 5/6 infection (2.7 x/divided by 1.6 U/mL). A selected group of 12 HIV-seropositive individuals (stages 1, 2, and 3) who harbored HIV capable of replicating in T cells but not in monocyte cultures had a mean serum IL-6 level of 5.3 U/mL (x/divided by 1.5), a value significantly lower (P less than .004) than that measured in control HIV-seropositive individuals infected with monocytropic HIV (39 x/divided by 1.9 U/mL). In addition, serum IL-6 levels in HIV-seropositive individuals (stages 1 through 6) correlated directly with serum immunoglobulin G (IgG) levels (R = .74, P less than .001). Monocytes but not T cells are capable of a high level IL-6 production in vitro, and monocyte-derived IL-6 stimulates Ig production in activated B cells. Thus, HIV-seropositive individuals who often are infected with monocytotropic HIV and often display abnormally elevated serum IgG levels may exhibit these abnormalities as a consequence of abnormally elevated IL-6 levels induced by HIV.
Birx
D L
DL
Division of Retrovirology, Walter Reed Army Institute of Research, Washington DC.
Redfield
R R
RR
Tencer
K
K
Fowler
A
A
Burke
D S
DS
Tosato
G
G
D002478:Cells, Cultured; D006678:HIV / Q000302:isolation & purification / Q000502:physiology*; D015658:HIV Infections / Q000378:metabolism* / Q000382:microbiology; D006679:HIV Seropositivity / Q000097:blood; D006801:Humans; D007074:Immunoglobulin G / Q000378:metabolism; D007376:Interleukin-2 / Q000494:pharmacology; D015850:Interleukin-6 / Q000096:biosynthesis* / Q000097:blood; D007963:Leukocytes, Mononuclear / Q000378:metabolism / Q000382:microbiology; D009000:Monocytes / Q000378:metabolism / Q000382:microbiology; D010835:Phytohemagglutinins / Q000494:pharmacology; D013601:T-Lymphocytes / Q000378:metabolism / Q000382:microbiology; D014779:Virus Replication
D007074:Immunoglobulin G; D007376:Interleukin-2; D015850:Interleukin-6; D010835:Phytohemagglutinins