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

Objective: To evaluate changes in serum levels of chemokines, chemokine pro duction, and chemokine receptor expression by peripheral blood mononuclear cells (PBMC), after treatment of HIV-1-infected individuals with interleuki n (IL)-2. Methods: We determined CC-chemokine levels by enzyme-linked immunosorbent a ssay and chemokine receptor expression using FAGS analysis or reverse trans criptase polymerase chain reaction in samples from patients receiving highl y active antiretroviral therapy (HAART) supplemented with low doses of reco mbinant IL-2, Results were compared with a control group of patients receiv ing HAART. Results: Serum levels of RANTES, macrophage inflammatory protein (MIP)-1 al pha 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 recept or (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-2 b 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 syst em. Only expression of CXCR-4 appears to increase, due in part to lymphocyt e activation. Therefore, the efficacy of IL-2 treatment in HIV-1 infection has to be evaluated by its ability to activate and induce faster regenerati on of the immune system. (C) 1999 Lippincott Williams & Wilkins.