EFFECTS OF HUMAN-IMMUNODEFICIENCY-VIRUS AND COLONY-STIMULATING FACTORS ON THE PRODUCTION OF INTERLEUKIN-6 AND TUMOR-NECROSIS-FACTOR-ALPHA BY MONOCYTE MACROPHAGES/

Patients infected with human immunodeficiency virus (HIV) frequently h ave increased production of interleukin 6 (IL-6) and tumor necrosis fa ctor alpha (TNF-alpha), and these cytokines may in turn contribute to the disease pathogenesis. It has been hypothesized that secretion of t hese cytokines by HIV-exposed mononuclear cells or HN-infected monocyt e/macrophages (M/Ms) is the principal source of their overproduction i n HIV-infected patients, and the present study was undertaken to explo re this issue, We observed that in the absence of endotoxin or cytokin es, M/Ms productively infected by HIV do not produce detectable IL-6 o r TNF-alpha, However, granulocyte-macrophage colony-stimulating factor (GM-CSF), a cytokine that enhances HIV replication in M/Ms and is fre quently used to propagate monocytotropic strains of HIV, can induce th e relatively long-term production of IL-6 (up to 47 U/ml) and TNF-alph a (up to 47 pg/ml) by M/Ms, even in the absence of HIV. Also, HIV indu ced production of a relatively small (less than or equal to 9 U/ml) qu antity of IL-6 in M/Ms stimulated with macrophage-colony stimulating f actor (M-CSF), Finally, while highly concentrated HIV induced producti on of both cytokines by either M/Ms or peripheral blood mononuclear ce lls (PBMCs), this production was almost completely eliminated when car e was taken to avoid contamination of HPV by endotoxin. These data sug gest that the excess IL-6 and TNF-alpha in HIV-infected patients does not simply result from their production by HIV-infected M/Ms and that alternative mechanisms are involved in this process.