Birx D L, Redfield R R, Tencer K, Fowler A, Burke D S, Tosato G
Division of Retrovirology, Walter Reed Army Institute of Research, Washington DC.
Blood. 1990 Dec 1;76(11):2303-10.
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.
白细胞介素-6（IL-6）是一种由单核细胞、成纤维细胞和其他细胞类型产生的多功能细胞因子，可由多种刺激物诱导产生，包括细菌、病毒和其他细胞因子。当正常单核细胞培养物暴露于人类免疫缺陷病毒（HIV）的嗜单核细胞株HTLV-IIIBa-L时，在培养12至43天后，在培养上清液中检测到显著水平的IL-6生物活性，此时有HIV产生的相关证据。同样，当正常单核细胞培养物与来自HIV感染个体的外周血单个核细胞共培养时，这些培养物中的HIV复制与IL-6的产生相关。在进一步的研究中，我们确定，与正常人（1.6×/除以1.2 U/mL）相比，处于1/2期感染（25.2×/除以1.8 U/mL）和3/4期感染（46.1×/除以1.7 U/mL）的HIV血清阳性个体的血清IL-6生物活性平均水平异常升高。相比之下，5/6期感染（2.7×/除以1.6 U/mL）患者的血清IL-6平均水平与正常水平无差异。一组选定的12名HIV血清阳性个体（1、2和3期），其携带的HIV能够在T细胞中复制，但不能在单核细胞培养物中复制，其血清IL-6平均水平为5.3 U/mL（×/除以1.5），该值显著低于（P小于0.004）在感染嗜单核细胞HIV的对照HIV血清阳性个体中测得的值（39×/除以1.9 U/mL）。此外，HIV血清阳性个体（1至6期）的血清IL-6水平与血清免疫球蛋白G（IgG）水平直接相关（R = 0.74，P小于0.001）。单核细胞而非T细胞能够在体外高水平产生IL-6，单核细胞衍生的IL-6刺激活化B细胞产生Ig。因此，经常感染嗜单核细胞HIV且经常表现出血清IgG水平异常升高的HIV血清阳性个体，可能由于HIV诱导的IL-6水平异常升高而出现这些异常。
