Chemokine and chemokine receptor expression after combined anti-HIV-1 interleukin-2 therapy

Objective: To evaluate changes in serum levels of chemokines, chemokine production, and chemokine receptor expression by peripheral blood mononuclear cells (PBMC), after treatment of HIV-1-infected individuals with interleukin (IL)-2. Methods: We determined CC-chemokine levels by enzyme-linked immunosorbent assay and chemokine receptor expression using FAGS analysis or reverse transcriptase polymerase chain reaction in samples from patients receiving highly active antiretroviral therapy (HAART) supplemented with low doses of recombinant IL-2, Results were compared with a control group of patients receiving HAART. Results: Serum levels of RANTES, macrophage inflammatory protein (MIP)-1 alpha and MIP-1 beta, and the production of these chemokines by unstimulated and stimulated PBMC, were not modified by IL-2 administration. In contrast, the IL-2-treated group showed increased expression of CXC-chemokine receptor (CXCR)-4 in the CD4 T-cell subset after 24 weeks of treatment, which was associated with increased mRNA levels. A lower increase was observed in CC-chemokine receptor (CCR)-5 expression by CD4 T cells. No modifications in the expression of these receptors were observed in monocytes and no general increases were observed in mRNA levels of chemokine receptors CCR-1, CCR-2b and CCR-3 in IL-2-treated patients. Conclusions: IL-2 at doses that significantly increase CD4 cell counts does not induce dramatic modifications in the chemokine/chemokine receptor system. Only expression of CXCR-4 appears to increase, due in part to lymphocyte activation. Therefore, the efficacy of IL-2 treatment in HIV-1 infection has to be evaluated by its ability to activate and induce faster regeneration of the immune system. (C) 1999 Lippincott Williams & Wilkins.