PHENCYCLIDINE EXPOSURE ALTERS IN-VITRO CELLULAR IMMUNE-RESPONSE PARAMETERS ASSOCIATED WITH HOST-DEFENSE

Phencyclidine hydrochloride (PCP) was tested for its ability to alter a variety of immune effector and regulatory functions in vitro. B6C3F1 , murine splenic lymphocytes or elicited peritoneal macrophages were c ultured in vitro with medium only or medium containing 10(-10)-10(-4) M PCP. Macrophages cultured with or without PCP were stimulated with l ipopolysaccharide, and production of interleukin 6 (IL-6) and tumor ne crosis factor (TNF) was assessed by bioassay. Cytotoxic T-cell effecto r function was determined following 5-day lymphocyte co-culture with t umor stimulator cells in the presence of PCP. In addition, the ability of T-lymphocytes to produce specific immunoregulatory cytokines IL-2 and IL-4 in the presence of PCP was quantitated by bioassay. B-lymphoc yte function was determined by quantitating lymphocyte proliferation f ollowing stimulation with anti-IgM antibody and murine IL-4. Natural i mmunity was assessed by culturing lymphocytes with or without PCP for 24 h, then quantitating basal and IL-2 augmented natural killer (NK) c ell activity. In the absence of effects on cell viability, significant suppression of IL-2 production by T-cells was noted at pharmacologica lly relevant PCP concentrations (1 muM). In vitro concentrations of 10 muM suppressed the generation of specifically sensitized cytotoxic T- cells. In addition, PCP significantly suppressed both IL-2-augmented N K function as well as B-lymphocyte proliferation. By comparison, macro phage IL-6 production was not affected by any concentration of PCP exa mined in this study.