Production of Tumor Necrosis Factor-Alpha and Interleukin-1 by Alveolar Macrophages from HIV-1-Infected Persons

Abstract

Tumor necrosis factor-alpha (TNF-α) and interleukin-1 (IL-1) are potent immunomodulatory cytokines which are produced principally by cells of the macrophage-monocyte lineage. We conducted an investigation to assess the secretion of these cytokines by bronchoalveolar macrophages from patients with progressive stages of human immunodeficiency virus (HIV-1) infection. The mean level of TNF-α produced by macrophages from 9 patients with AIDS was significantly reduced compared with the responses of macrophages from 6 healthy HIV-1-seronegative persons, 6 patients with either asymptomatic HIV-1 infection or persistent generalized lymphadenopathy, and 6 patients with AIDS-related complex (ARC). The four study groups did not differ in their mean IL-1β responses. However, within the HIV-1-infected patient population, macrophages from 4 patients, 3 of whom had AIDS and 1 with ARC, failed to secrete detectable levels of IL-1β. All 4 patients were also nonresponsive in assays for TNF-α. These data establish that advanced HIV-1 infection may result in a pronounced dysfunction in the cytokine responses of alveolar macrophages.