Induction of interleukin-6 during human immunodeficiency virus infection

Deborah L. Birx, Robert R. Redfield, Kathleen Tencer, Arnold Fowler, Donald S. Burke, Giovanna Tosato

Research output: Contribution to journalArticlepeer-review

Abstract

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 ×/÷ 1.8 U/mL) and stage 3/4 infection (46.1 ×/÷ 1.7 U/mL) when compared with normals (1.6 ×/÷ 1.2 U/mL). In contrast, mean serum IL-6 levels were not different from normal in stage 5/6 infection (2.7 ×/÷ 1.6 U/mL). A selected group of 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 (×/÷ 1.5), a value significantly lower (P <.004) than that measured in control HIV-seropositive individuals infected with monocytropic HIV (39 ×/÷ 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 <.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.

Original languageEnglish (US)
Pages (from-to)2303-2310
Number of pages8
JournalBlood
Volume76
Issue number11
StatePublished - Dec 1 1990
Externally publishedYes

ASJC Scopus subject areas

  • Hematology

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