EXPRESSION OF IL-10, IL-4 AND INTERFERON-GAMMA IN UNSTIMULATED AND MITOGEN-STIMULATED PERIPHERAL-BLOOD LYMPHOCYTES FROM HIV-SEROPOSITIVE PATIENTS

Infection of immune cells with HIV induces dysregulation of cytokines which may play a vital role in HIV pathogenesis. We analysed the expression of T helper type 1 (Thl) (interferon-gamma (IFN-gamma)) and Th2 (IL-4, IL-10) type cytokines in peripheral blood lymphocytes (PBL) from HIV+ patients. The semiquantitative reverse transcriptase polymerase chain reaction (RT-PCR) analysis revealed that IFN-gamma mRNA in unstimulated PBL was significantly decreased and IL-IO mRNA was significantly upregulated in patients with < 400 CD4(+) T cells/mm(3) (n = 30) as compared to patients with > 400 CD4(+) T cells/mm(3) (n = 6) and normal controls (n = 16). In addition, IL-10 mRNA levels were inversely associated with IFN-gamma expression. Similar results were obtained by measuring IL-IO production in the supernatants of PBL cultured in vitro without stimulation by employing an enzyme immunosorbent assay (ELISA). However, the levels of IL-4 and IFN-gamma produced by unstimulated PBL were undetectable by ELISA. Mitogen stimulation of PBL revealed two groups of HIV+ individuals based on IL-10 production. PBL from one set of individuals produced low levels of IL-10 (low IL-IO producers) whereas the other group produced IL-IO comparable to that of normal controls (IL-10 producers). Production of IL-4 was significantly reduced in HIV+ individuals with < 400 CD4(+) T cells/mm(3) as compared to the normal controls. However, ability to produce IFN-gamma by mitogen-stimulated total PBL and CD4(+) purified cells was not impaired in HIV+ individuals. These results suggest that unstimulated and mitogen-stimulated PBL of HIV+ individuals exhibit dysregulation of Th2 type cytokines which may play a role in HIV immunopathogenesis.