N-ACETYLCYSTEINE (NAC) ENHANCES INTERLEUKIN-2 BUT SUPPRESSES INTERLEUKIN-4 SECRETION FROM NORMAL AND HIV-CELLS( CD4(+) T)

We find that purified CD4(+) T cells from 30 HIV+ individuals have a s uppressed Interleukin-4 (IL-4) production compared to normal controls regardless of activator (anti-CD3 or Con A) or co-activator [phorbol e ster (PMA or anti-CD28)], generally by 2-4 fold. In every case, the ce lls producing IL-4 respond more strongly to anti-CD28 co-activation th an to PMA, ie, 1150 pg/ml compared to 2070 pg/ml for controls and 398 pg/ml compared to 1250 pg/ml for HIV+ cells, respectively. In contrast , anti-CD3 with PMA gives a more vigorous IL-2 response than with anti -CD28, ie, 37.3 ng/ml compared to 12.3 ng/ml for controls and 28.5 ng/ ml versus 15.1 ng/ml for HIV+ cells, respectively. These data are not compatible with the T(H)1/T(H)2 switch hypothesis since IL-4 productio n is decreased, not increased for CD4(+) HIV+ T-cells and while IL-2 p roduction is decreased with PMA, it is not decreased significantly wit h anti-CD28. Interestingly, 5 mM N-acetylcysteine (NAC) acts as an imm unoenhancer; mitogenesis was enhanced 2 fold or more in general for co ntrol and HIV(+)CD4(+) T-cells and IL-2 production was enhanced 2-3 fo ld for anti-CD3 (with PMA or anti-CD28) for both controls and HIV+ CD4 (+) cells. However, NAC suppressed IL-4 production induced by anti-CD3 and anti-CD28 in both control and HIV+ CD4(+) T cells. In the other c ases, it produced in general no significant change. Our data show that both IL-2 and IL-4 production tend to be unchanged or depressed in th e HIV+ state of the CD4(+) population, and are affected differently by NAC, ie, mitogenesis and IL-2 are enhanced 2-3 fold, but IL-4 product ion is either unchanged or suppressed, particularly with anti-CD28 co- activation.