Thalidomide's ability to augment the synthesis of IL-2 in vitro in HIV-infected patients is associated with the percentage of CD4+cells in their blood

Thalidomide is used for treating erythema nodosum leprosum. It is also used to treat aphthous ulcers in HIV-infected patients. The mechanism of action of this drug is yet to be fully understood, but modulation of inflammatory cytokines like IL-2 and TNF-alpha may play a role. We investigated the eff ect of thalidomide on the production of IL-2 and TNF-alpha by staphylococca l enterotoxin A (SEA) stimulated peripheral blood mononuclear cells (PBMC) from HIV-infected patients. The PBMC from 20 patients was incubated in the presence of 4.0 mu g/ml of thalidomide and 50 ng/ml of SEA. After 18 h, the culture supernatant was assayed for IL-2 and TNF-alpha. The PBMC incubated with thalidomide and SEA produced significantly more IL-2 than those incub ated with SEA alone. The TNF-alpha secreted by the same cells incubated wit h thalidomide and SEA was not significantly different from that secreted by the cells incubated with SEA alone. The amount of IL-2 produced in the tha lidomide and SEA treated cultures was directly correlated with the percenta ge of CD4+ cells in blood, and inversely correlated with the percentage of CD8+ cells in blood. No statistically significant correlations were found w hen comparing the amount of TNF-alpha produced in the thalidomide and SEA t reated cultures with the percentage of CD4+ or CD8+ cells in the blood. Tha lidomide can act, in vitro, as an additional stimulant to augment the synth esis of IL-2 in HIV-infected patients. Increased production of IL-2 by acti vated T-cells may be a mechanism through which it exerts its immunomodulato ry effects. (C) 2000 Published by Elsevier Science B.V. All rights reserved .