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Plasma Cytokines, Cytokine Antagonists, and Disease Progression in African Women Infected with HIV-1.
Thea, Donald M. MD; Porat, Reuven MD; Nagimbi, Khondi MD; Baangi, Matela MD; St. Louis, Michael E. MD; Kaplan, Gilla PhD; Dinarello, Charles A. MD; Keusch, Gerald T. MD
[Miscellaneous] Annals of Internal Medicine. 124(8):757-762, April 15, 1996.

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Objectives: To examine the relation of circulating cytokines and cytokine antagonists to the progression of human immunodeficiency virus type 1 (HIV-1) disease.

Design: Cross-sectional analysis.

Setting: An ambulatory acquired immunodeficiency syndrome (AIDS) research clinic in Kinshasa, Zaire.

Patients: 48 women with AIDS, 51 women with HIV infection who were clinically asymptomatic, and 11 female controls who did not have HIV infection, all from Zaire.

Measurements: Plasma levels of interleukin-1 beta, tumor necrosis factor-alpha (TNF-alpha), interleukin-6, interleukin-8, interferon-gamma, interleukin-1 beta receptor antagonist (interleukin-1Ra), and TNF soluble receptor p55 (TNFsRp55) were assayed by specific radioimmunoassays. Plasma levels of interferon-gamma were assayed by commercial enzyme-linked immunosorbent assay. The Wilcoxon rank-sum test was used to assess the significance of mean and 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 were seen in any of the 11 controls. Median values of interleukin-1 beta (320 pg/mL), TNF-alpha (210 pg/mL), and interleukin-8 (750 pg/mL) were elevated in HIV-infected asymptomatic patients compared with patients with AIDS (2-, 2.6-, and 18.7-fold higher, respectively; P less than 0.001). Interleukin-1Ra and TNFsRp55 levels were substantially higher than interleukin-1 beta and TNF-alpha levels in HIV-infected asymptomatic patients (73- and 14-fold, respectively) and were higher than those in patients with AIDS (17.8- and 1.74-fold, respectively).

Conclusion: High circulating levels of the proinflammatory cytokines interleukin-1 beta and TNF-alpha, combined with an excess of their natural inhibitors interleukin-1Ra and TNF-sRp55, were seen in clinically asymptomatic HIV-1-positive African women but not in African women with AIDS or in HIV-negative controls. Circulating cytokine antagonists may play a clinical role in modulating cytokine-associated symptoms in the early phases of HIV infection.

Ann Intern Med.1996;124:757-762.