Quantitative analysis of serum IL-6 and its correlation with increased levels of serum IL-2R in HIV-induced diseases.
We have devised a luminescence sandwich ELISA for the quantification of IL-6 in both sera and cell culture supernatants, which had a detection limit of 100 fg/ml of test sample. By using the luminescence sandwich-ELISA, low but measurable levels of IL-6 (9.5 pg/ml on average) were found in the sera from normal individuals. The serum levels of IL-6 were elevated in HIV-seropositive asymptomatic carriers (55.5 pg/ml on average), and the IL-6 levels were correlated with the degree of HIV-induced disease progression (AIDS-related complex 106.8 pg/ml on average and (AIDS 283 pg/ml). IL-6 immunoreactivity in the sera of AIDS patients eluted at a 25,000 m.w. major peak, which was biologically active and heat-stable, and a 500,000 m.w. minor peak in size-exclusion HPLC. Interestingly, a significant correlation was observed between the serum IL-6 levels and soluble IL-2R levels. In vitro, HIV infection of PHA-activated PBMC led to enhanced release of IL-6 into the culture supernatants. Moreover, soluble IL-2R release was markedly increased by adding exogenous IL-6, whereas it was decreased by adding the neutralizing anti-IL-6 mAb to the cultures. These results demonstrate that increased IL-6 levels are significantly associated with sIL-2R levels, and suggest a cause of the increased levels of this receptor in patients with HIV infection. Furthermore, both serum IL-6 and serum IL-2R levels in HIV infection reflect the stage of the HIV-induced disease.
Honda
M
M
AIDS Research Center, National Institute of Health, Tokyo, Japan.
Kitamura
K
K
Mizutani
Y
Y
Oishi
M
M
Arai
M
M
Okura
T
T
Igarahi
K
K
Yasukawa
K
K
Hirano
T
T
Kishimoto
T
T
D002478:Cells, Cultured; D004797:Enzyme-Linked Immunosorbent Assay; D015658:HIV Infections / Q000097:blood*; D006801:Humans; D066298:In Vitro Techniques; D015850:Interleukin-6 / Q000096:biosynthesis / Q000097:blood* / Q000276:immunology; D015375:Receptors, Interleukin-2 / Q000097:blood* / Q000378:metabolism; D012995:Solubility
D015850:Interleukin-6; D015375:Receptors, Interleukin-2