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Ann Intern Med. 1996 Apr 15;124(8):757-62.

Plasma cytokines, cytokine antagonists, and disease progression in African women infected with HIV-1.

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New England Medical Center, Boston, Massachusetts, USA.



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


Cross-sectional analysis.


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


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.


Plasma levels of interleukin-1beta, tumor necrosis factor-alpha (TNF-alpha), interleukin-6, interleukin-8, interferon-gamma, interleukin-1beta 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.


Of the 48 patients with AIDS, circulating interleukin-1beta 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-1beta (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 < 0.001). Interleukin-1Ra and TNFsRp55 levels were substantially higher than interleukin-1beta 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).


High circulating levels of the proinflammatory cytokines interleukin-1beta 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.


At an outpatient AIDS research clinic in Kinshasa, Zaire, physicians conducted a medical examination and took blood samples from 48 women with AIDS, 51 women with asymptomatic HIV-1 infection, and 11 healthy HIV-1 seronegative women to study the relationship of circulating cytokines and cytokine antagonists to the progression of HIV-1 infection. Asymptomatic HIV-1-infected women had higher levels of the cytokines interleukin-1beta and tumor necrosis factor-alpha (TNF-alpha) than AIDS cases and controls (320 vs. 156 pg/ml, p 0.001, and 210 vs. 78 pg/ml, p 0.001, respectively) and even higher levels of interleukin-1Ra and TNFsRp55 (both natural cytokine antagonists) (4300 vs. 100 pg/ml, p 0.001; and 12,500 vs. 1450 for the AIDS group [p 0.0001] and 950 for controls [p 0.001]). The high levels of the two proinflammatory cytokines in asymptomatic HIV-1 infected women suggests that the high levels of antagonist cytokines blocked the clinical effects of interleukin-1beta and TNF-alpha. 46 AIDS patients had no detectable interleukin-1beta. 42 AIDS patients had no detectable TNF-alpha. The lack of cytokines in most AIDS patients suggests that persons in end-stage HIV-1 disease have a limited capacity to synthesize cytokines, perhaps depleting the remaining cytokine-producing central and peripheral lymphoid tissues. Asymptomatic HIV-1-infected women also had higher levels of interleukin-8 than AIDS cases and controls (750 vs. 40 pg/ml; p 0.001). 11 of the 13 highest values of interferon-gamma (11 pg/ml) belonged to AIDS patients rather than asymptomatic HIV-1-infected cases (p = 0.005). In the last 2 months, AIDS patients with detectable interferon-gamma had fever of longer duration than those with no interferon-gamma (17 vs. 9 days, p = 0.05), indicating that AIDS cases with interferon-gamma were still capable of responding to inflammatory stimuli. These findings suggest that cytokine antagonists may modulate cytokine-associated symptoms in the early phases of HIV-1 infection.

[Indexed for MEDLINE]

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