Plasma Cytokines, Cytokine Antagonists, and Disease Progression in African Women Infected with HIV-1

doi:10.1059/0003-4819-124-8-199604150-00009

Plasma Cytokines, Cytokine Antagonists, and Disease Progression in African Women Infected with HIV-1

From the New England Medical Center, Boston, Massachusetts; International Collaboration in AIDS Research Unit and Ministry of Health, Kinshasa, Zaire; Centers for Disease Control and Prevention, Atlanta, Georgia; and Rockefeller University, New York, New York. Acknowledgments: The authors thank Sabine deBreuker for technical assistance in laboratory assays of cytokines, the Zairian laboratory staff headed by Atido Avoyo for dedicated service to the project and their countrymen, and our patients for their willing involvement in these studies, which were prematurely terminated because of extreme social and political problems in Zaire. Grant Support: By International Collaboration in AIDS Research Program project grant PO1-AI-26698 and National Institute of Allergy and Infectious Diseases research grants AI-15614, AI-24775, and AI-07012. Requests for Reprints: Gerald T. Keusch, MD, Division of Geographic Medicine and Infectious Diseases, New England Medical Center, 750 Washington Street, Box 041, Boston, MA 02111. Current Author Addresses: Drs. Thea, Porat, Dinarello, and Keusch: Division of Geographic Medicine and Infectious Diseases, New England Medical Center, 750 Washington Street, Boston, MA 02111.

Abstract

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 β, tumor necrosis factor-α (TNF-α), interleukin-6, interleukin-8, interferon-γ, interleukin-1 β receptor antagonist (interleukin-1Ra), and TNF soluble receptor p55 (TNFsRp55) were assayed by specific radioimmunoassays. Plasma levels of interferon-γ 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 β was detected in 2, TNF-α 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 β (320 pg/mL), TNF-α (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 < 0.001). Interleukin-1Ra and TNFsRp55 levels were substantially higher than interleukin-1 β and TNF-α 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 β and TNF-α, 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.