Induction of interleukin-6 during human immunodeficiency virus infection

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 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.

Defective IL-6 secretion in HIV-infected haemophilia patients

“…As in previous studies [26][27][28] we found elevaied mean plastna IL-6 levels in HI V-infeeled patients. However, most of our HI Vinfeeted palients (7S% of Group 2 and 47".. of Group 3 palienis) had no delectable 1 L-6 levels.…”

“…HIV-infected patients elevated serum or plasma 1 L-6 levels were described in several studies [26 28]. Birx et al [28] described serum IL-6 levels to be correlated with serum [gG levels. Amadori et iil.…”

Heat shock-enhanced T cell apoptosis with heat shock protein 70 on T cell surface in multicentric Castleman's disease

“…Atrophy of the T cell-dependent areas in the lymph nodes of MCD has already been reported [26], and data from our group show that the immunological disturbances in MCD were similar to those seen in HIV infection in Table 1 and [5]. Thus T cell dysfunction, NK cell dysfunction, polyclonal B cell activation, and dysregulation of IL-6 secretion by monocytes are features of both MCD and HIV infection [27][28][29][30]. In MCD patients, cell dysfunction also results in apoptosis [9], a shared feature of HIV infection [24,[31][32][33].…”

Immune dysregulation to Ethiopian immigrants in Israel: relevance to helminth infections?

“…For determination of IL-6 activity in plasma, B9 cells were used in a standard assay as described [11]. Briefly, serial dilutions of heat-inactivated plasma samples and recombinant Escherichia coli-derived IL-6 (Amersham, Aylesbury, UK) were distributed to 96-well flat-bottomed plates (Nunc).…”