Differences in cytokine secretion by intestinal mononuclear cells, peripheral blood monocytes and alveolar macrophages from HIV-infected patients

Mononuclear cells of the lamina propria (LpMNC), isolated from endoscopically taken biopsies of the large bowel from AIDS patients, were analysed for their ability to secrete tumour necrosis factor alpha (TNF-α), IL-1β and IL-6. Stimulation of LpMNC from normal controls with pokeweed mitogen (PWM) led to a time- and dose-dependent enhancement of TNF-α, IL-1β and IL-6 secretion. In contrast, PWM stimulation of LpMNC from AIDS patients resulted in only a small increase in TNF-α release. Constitutive secretion of IL-1β and IL-6 in these patients was already increased to the concentration range of stimulated cells from normal controls and could not be further increased, probably due to maximal in vivo stimulation. Secretion of TNF-α, IL-1β and IL-6 by peripheral blood monocytes (PBM) and alveolar macrophages from AIDS patients was elevated with or without stimulation compared with normal controls. Obviously, the regulation of TNF-α secretion is dependent on the microenvironment. Since it is known that interferon-gamma (IFN-γ) may induce the production of TNF-α, the secretion of this cytokine was examined. Release of IFN-γ was constitutively and under stimulation lowered in LpMNC from AIDS patients compared with normal controls. Addition of IFN-γ to LpMNC did not result in enhanced TNF-α secretion. Our data indicate a defective function of intestinal mononuclear cells in AIDS patients as shown by the diminished TNF-α secretion.