Circulating Levels of Stromal Cell-Derived Factor 1α and Interleukin 7 in HIV Type 1 Infection and Pulmonary Tuberculosis Are Reciprocally Related to CXCR4 Expression on Peripheral Blood Leukocytes

Abstract

In sub-Saharan Africa the coincidence of HIV-1 and Mycobacterium tuberculosis coinfection is ever-increasing, this being associated with increased progression to disease and reduced patient survival. Raised plasma levels of stromal cell-derived factor (SDF)-1α and interleukin (IL)-7, cytokines important in T cell development, and in the modulation of surface CXCR4 expression, have been reported to be associated with HIV-1 disease progression. We have previously shown specific disease group-related down modulation in vivo of the SDF-1 ligand, CXCR4, in HIV-1-seropositive patients, patients with pulmonary tuberculosis, and patients coinfected with M. tuberculosis and HIV-1. In this study, both SDF-1α and IL-7 plasma levels were significantly elevated from normal in similar disease groups (p < 0.001). Both SDF-1α and IL-7 plasma levels correlated negatively with the percentage of all subsets of leukocytes expressing CXCR4, across the study groups regardless of the presence or absence of disease. This suggests that CXCR4 receptors are likely modulated in similar ways by increased levels of these cytokines, even though the underlying mechanism of their increased production is likely to be different. In addition, plasma levels of SDF-1α correlated negatively with percentage of CD4⁺ T cells, and both SDF-1α and IL-7 levels correlated positively with plasma HIV-1 viral load. Collectively, these results confirm a role for SDF-1α and IL-7 in HIV-1 disease progression, and suggest that these cytokines play a role in the modulation of CXCR4.