EFFECTS OF SUBCUTANEOUS INTERLEUKIN-2 THERAPY ON CD4 SUBSETS AND IN-VITRO CYTOKINE PRODUCTION IN HIV PLUS SUBJECTS

HIV infection is characterized by the reduction of the CD4+, CD45RA+, CD26+, and CD28+ lymphocyte subsets and of the in vitro production of IL-2, IL-4, and interferon-gamma; on the contrary, chemokine productio n is usually increased. These abnormalities are only partially restore d by antiretroviral chemotherapy. Therapy with interleukin-2 has been proposed to restore the functions of the immune system, but the mechan isms by which IL-2 exerts its activities are unknown. The aim of this study was to define the effects of rIL-2 administration on CD4+, CD45R A+, CD45R0+, and CD26+ lymphocytes and on the in vitro production of I L-2, IL-4, IL-10, IFN-gamma, RANTES, and sCD30 in HIV+ patients. 10 HI V+ patients with CD4 cell counts between 200 and 500 cells/mm(3) were treated with six cycles of subcutaneous recombinant IL-2 administratio n, in combination with zidovudine and didanosine. This therapeutic reg imen resulted in a remarkable increase in the number of CD4+ cells and in the prolonged reduction of the levels of viremia. CD45R01 cells we re expanded during the first cycle of therapy, while CD45RA+/CD26+ cel ls predominated after the third cycle. At this time, the in vitro prod uction of IL-2, IL-4, IFN-gamma, and sCD30 were significantly upregula ted. These results demonstrate that rIL-2 in HIV+ patients induces the reconstitution of the CD4/CD45RA lymphocytes subtype. This expanded c ell population recovered the ability to produce in vitro IL-2, IL-4, a nd IFN-gamma. These effects may be beneficial to HIVS patients by impr oving their immune response to microorganisms or vaccines.