Contribution of prostaglandin (PG) E2 to the IL-12 defect in HIV-infected (HIV+) patients

PG act as modulators of cytokine secretion of human T helper lymphocytes and inhibit the production of IL-12 by monocytes. IL-12 production by PBMC from HIV⁺ donors is appreciably reduced; in contrast, PGE2 release is increased. We investigated whether increased PG synthesis represents one mechanism involved in the decreased IL-12 production in HIV+ patients. We studied the in vitro effect of an inhibitor of PG synthesis, indomethacin (IM), on IL-12 production by 5. aureus Cowan strain 1 (SAC)-stimulated PBMC from 31 HIV+ donors (CD4⁺: Range: 3 to 976//d). IM-treated cells produced a 4-fold mean greater amount of IL- 12 than untreated cells (22.6 vs 9.2 pg/ml. p< 0.05, U-test). However, the response was heterogenous. PGE2 production was decreased by IM treatment to the same extent in cells from patients whose IL-12 production was or was not improved (p>0.05, U-test). IM treatment of PBMC from HIV⁺ patients led to a 35-fold decrease of PGE2 production (273 vs 8352 pg/ml, p<0.05, U-test). When patients were classified by clinical staging, more of those who responded belonged to the less symptomatic A and B stages (10 of 19) than the C stage (4 of 12). IM had no effect on IL-10 production (1524 vs 1784 pg/ml). These results show that hyper production of PGE2 contributes to the impairment of IL-12 production in HIV+ patients. However, blockade of PG pathway is not sufficient to fully correct the defective IL-12 production.