TH1 AND TH2 CYTOKINE PRODUCTION BY PERIPHERAL-BLOOD MONONUCLEAR-CELLSFROM HIV-INFECTED PATIENTS

Objective: To study the TH1->TH2 cytokine switch, thought to occur dur ing the progression of HIV infection. Design: We investigated interleu kin (IL)-2, interferon (IFN)-gamma, IL-4, IL-6 and IL-10 production by phytohaemagglutinin (PHA)-stimulated and unstimulated peripheral bloo d mononuclear cell (PBMC) cultures from HIV-negative controls and HIV- positive subjects, stratified according to the Centers for Disease Con trol and Prevention (CDC) criteria. We correlated the above parameters with markers of disease progression. Methods: Cytokine production was measured in supernatants using enzyme-linked immunosorbent assay (ELI SA) in 40 patients and 17 controls. To evaluate disease progression, w e also determined CD4+ cell counts, PHA-induced proliferative response , p24 release and spontaneous immunoglobulin (Ig)G and IgM production. Results: In agreement with the TH1->TH2 switch hypothesis, we found th at in the course of HIV disease mitogen-stimulated IL-2 production dec reased, spontaneous and stimulated IL-6 production and spontaneous IL- 10 secretion increased; IL-4 showed an increasing trend, although it w as reduced in HIV-positive subjects. Finally, immunoglobulin productio n increased over time. In contrast, mitogen-stimulated IFN-gamma and I L-10 production did not change among the CDC categories, although the former decreased and the latter increased in comparison with HIV-negat ive controls. Conclusions: Our data partially agree with the TH1->TH2 switch hypothesis. Since IL-6 and IL-10 are produced by different cell types, whose proportions and functional features vary in the course o f the disease, further experiments with purified lymphocyte subsets an d monocytes are required. Nevertheless, as already suggested, we belie ve that a switch from a type 1 to a type 2 response occurs in HIV infe ction.