title: Circulating levels of stromal cell-derived factor 1alpha 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)-1alpha 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-1alpha and IL-7 plasma levels were significantly elevated from normal in similar disease groups (p < 0.001). Both SDF-1alpha 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-1alpha correlated negatively with percentage of CD4(+) T cells, and both SDF-1alpha and IL-7 levels correlated positively with plasma HIV-1 viral load. Collectively, these results confirm a role for SDF-1alpha and IL-7 in HIV-1 disease progression, and suggest that these cytokines play a role in the modulation of CXCR4.
authors.affiliation: AIDS Virus Research Unit, National Institute for Communicable Diseases, University of the Witwatersrand, Johannesburg, South Africa.
authors.forename: Sharon
authors.initials: S
authors.lastname: Shalekoff
authors.forename: Caroline T
authors.initials: CT
authors.lastname: Tiemessen
mesh_terms: D000328:Adult; D000368:Aged; D054377:Chemokine CXCL12; D019743:Chemokines, CXC / Q000097:blood*; D018450:Disease Progression; D015658:HIV Infections / Q000097:blood / Q000150:complications / Q000276:immunology* / Q000503:physiopathology; D015497:HIV-1 / Q000472:pathogenicity; D006801:Humans; D015851:Interleukin-7 / Q000097:blood*; D007963:Leukocytes, Mononuclear / Q000378:metabolism*; D008875:Middle Aged; D009169:Mycobacterium tuberculosis; D019718:Receptors, CXCR4 / Q000097:blood*; D014397:Tuberculosis, Pulmonary / Q000097:blood / Q000150:complications / Q000276:immunology* / Q000503:physiopathology
chemical_list: C515255:CXCL12 protein, human; D054377:Chemokine CXCL12; D019743:Chemokines, CXC; D015851:Interleukin-7; D019718:Receptors, CXCR4