Cytokines and Soluble Receptor Changes in the Transition from Primary to Early Chronic HIV Type 1 Infection

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Abstract
We studied determinants of chronic inflammation and/or immune activation in plasma from patients in the transition from primary to early chronic HIV-1 infection. The following parameters were estimated in seven patients over time: plasma concentrations of soluble CD8 (sCD8), tumor necrosis factor alpha (TNF-alpha), soluble TNF receptor type II (sTNFRII), interleukin 6 (IL-6), soluble IL-6 receptor (sIL6R), IL-10, transforming growth factor beta1 (TGF-beta1), along with CD4- and CD8-positive T cell counts, p24 antigenemia, and clinical evaluation. Results showed that concentrations of sCD8, TNF-alpha, and sTNFRII, and peripheral CD8-positive lymphocyte counts, were significantly increased in patients, compared to HIV-negative controls, and showed a trend toward normal values over time. Levels of IL6, sIL6R, IL-10, and TGF-beta1 did not differ from those of controls and did not change over time. Heterogeneity was observed among the patients in terms of CD4-positive T cell depletion, levels of sCD8, concentrations of TNF-alpha/sTNFRII, and clinical outcome. These data indicate that in the transition phase from primary acute to chronic and asymptomatic infection the host immune activation in response to the virus is highly heterogeneous and that the sustained rise in TNF-alpha and its receptor may represent an important therapeutic target in early disease. The persistence of a state of chronic inflammation and/or immune activation could influence the progression of disease independently from CD4-positive T cell counts.