PLASMA CYTOKINES, CYTOKINE ANTAGONISTS, AND DISEASE PROGRESSION IN AFRICAN WOMEN INFECTED WITH HIV-1

Objectives: To examine the relation of circulating cytokines and cytok ine antagonists to the progression of human immunodeficiency virus typ e 1 (HIV-1) disease. Design: Cross-sectional analysis. Setting: An amb ulatory acquired immunodeficiency syndrome (AIDS) research clinic in K inshasa, Zaire. Patients: 48 women with AIDS, 51 women with HIV infect ion who were clinically asymptomatic, and 11 female controls who did n ot have HIV infection, all from Zaire. Measurements: Plasma levels of interleukin-1 beta, tumor necrosis factor-alpha (TNF-alpha), interleuk in-6, interleukin-8, interferon-gamma, interleukin-1 beta receptor ant agonist (interleukin-1Ra), and TNF soluble receptor p55 (TNFsRp55) wer e assayed by specific radioimmunoassays. Plasma levels of interferon-g amma were assayed by commercial enzyme-linked immunosorbent assay. The Wilcoxon rank-sum test was used to assess the significance of mean an d median differences between groups. Results: Of the 48 patients with AIDS, circulating interleukin-1 beta was detected in 2, TNF-alpha in 4 , interleukin-6 in 3, and interleukin-8 in 12. None of these factors w ere seen in any of the 11 controls. Median values of interleukin-lp (3 20 pg/ml), TNF-alpha (210 pg/mL), and interleukin-8 (750 pg/mL) were e levated in HIV-infected asymptomatic patients compared with patients w ith AIDS (2-, 2.6-, and 18.7-fold higher, respectively; P < 0.001). In terleukin-1Ra and TNFsRp55 levels were substantially higher than inter leukin-1 beta and TNF-alpha levels in HIV-infected asymptomatic patien ts (73- and 14-fold, respectively) and were higher than those in patie nts with AIDS (17.8- and 1.74-fold, respectively). Conclusion: High ci rculating levels of the proinflammatory cytokines interleukin-1 beta a nd TNF-alpha, combined with an excess of their natural inhibitors inte rleukin-1Ra and TNFsRp55, were seen in clinically asymptomatic HIV-1-p ositive African women but not in African women with AIDS or in HIV-neg ative controls. Circulating cytokine antagonists may play a clinical r ole in modulating cytokine-associated symptoms in the early phases of HIV infection.