DIFFERENTIAL-EFFECTS OF INTERLEUKIN-12, INTERLEUKIN-15, AND INTERLEUKIN-2 ON HUMAN-IMMUNODEFICIENCY-VIRUS TYPE-1 REPLICATION IN-VITRO

Cytokines may have clinical utility as therapeutic agents for human im munodeficiency virus type 1 (HIV-1) infection and as an adjuvant for v accines. The effect of interleukin-12 (IL-12) and IL-15 on in vitro HI V-1 replication was investigated. IL-12 and IL-15 at doses up to 10 ng /ml had little effect on basal HIV-1 p24 antigen production by chronic ally HIV-infected T (ACH-2) and monocytic (U1) cell lines. For ACH-2 c ells stimulated with phorbol 12-myristate 13-acetate (PMA; 50 ng/ml), IL-12 and IL-15 significantly increased p24 antigen production by 20 a nd 30%, respectively (n = 6). In contrast, IL-12 and IL-15 (10 ng/ml) treatment of PMA-stimulated U1 cells decreased p24 antigen production by 16 and 15%, respectively (n = 6). We next studied the effect of IL- 12 and IL-15 on HIV-infected peripheral blood mononuclear cells (PBMCs ). in 10 HIV-seropositive patients' PBMCs cocultured with mitogen-acti vated HIV-seronegative donor cells, two patterns of p24 antigen produc tion were observed in response to IL-2: low (p24 antigen production < 10(3) pg/ml; n = 8) and high (p24 antigen production > 10(3) pg/ml; n = 2) response. For the low-response pattern, IL-12 and IL-15 increased viral replication by 97-fold and 100-fold, respectively (P = 0.05 and 0.004, respectively). For the high-response pattern, both IL-12 and I L-15 suppressed HIV replication. The effect of IL-2, IL-12, and IL-15 on acute in vitro infection by HIV-1(JRCSF) was also examined. IL-12 d id not increase p24 antigen production above basal levels while IL-2 a nd IL-15 significantly enhanced p24 antigen production (by similar to 2-fold). In conclusion, IL-12 and IL-15 may have differential effects on latent and acute HIV infection, and their ability to enhance HIV pr oduction may depend on cell activation, Thus, the use of these cytokin es may be dictated by the clinical state of the patient.