INCREASED SPONTANEOUS SECRETION OF INTERLEUKIN-6 AND TUMOR-NECROSIS-FACTOR-ALPHA BY PERIPHERAL-BLOOD LYMPHOCYTES OF HUMAN IMMUNODEFICIENCY VIRUS-INFECTED CHILDREN

Interleukin 6 (IL-6) and tumor necrosis factor alpha (TNF-alpha) have been implicated in the transition of nonreplicating latent human immun odeficiency virus (HIV) infection to the replicating state of producti ve infection. In HIV infection increased concentrations of these cytok ines in serum have also been found in association with hypergammaglobu linemia. We have analyzed the ability of peripheral blood mononuclear cells (PBMC) of HIV-infected children to secrete IL-6 and TNF-alpha. I n kinetic studies, optimum spontaneous IL-6 secretion by 1 x 10(6) PBM C was achieved at 24 hours. The mean spontaneous IL-6 and TNF-alpha co ncentrations secreted by PBMC of known HIV-infected children (age rang e, 8 months to 11 years) were 1686 and 131 pg/ml, respectively, compar ed with 56 and 45 pg/ml, respectively, in normal healthy controls. No significant correlation was observed between spontaneously secreted IL -6 and TNF-alpha in culture supernatants with CD4 or CD8 numbers; with serum IgG, IgA and IgM concentrations; or with lymphoproliferative re sponses to recall antigens. There was, however, an association between ability to secrete IL-B with HIV-specific in vitro antibody productio n. Spontaneous IL-6 secretion decreased transiently after initiation o f antiretroviral therapy, returning to original values with continued treatment. Cytokine derangement in HIV-infected children includes PBMC -derived spontaneous IL-6 and TNF-alpha secretion.