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 cultured in vitro with medium only or medium containing 10(-10)-10(-4) M PCP. Macrophages cultured with or without PCP were stimulated with lipopolysaccharide, and production of interleukin 6 (IL-6) and tumor necrosis factor (TNF) was assessed by bioassay. Cytotoxic T-cell effector function was determined following 5-day lymphocyte co-culture with tumor 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-lymphocyte function was determined by quantitating lymphocyte proliferation following stimulation with anti-IgM antibody and murine IL-4. Natural immunity was assessed by culturing lymphocytes with or without PCP for 24 h, then quantitating basal and IL-2 augmented natural killer (NK) cell activity. In the absence of effects on cell viability, significant suppression of IL-2 production by T-cells was noted at pharmacologically relevant PCP concentrations (1 microM). In vitro concentrations of 10 microM suppressed the generation of specifically sensitized cytotoxic T-cells. In addition, PCP significantly suppressed both IL-2-augmented NK function as well as B-lymphocyte proliferation. By comparison, macrophage IL-6 production was not affected by any concentration of PCP examined in this study.
Thomas
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PT
Life Sciences Research, IIT Research Institute, Chicago, Illinois 60616.
House
R V
RV
Bhargava
H N
HN
D000818:Animals; D000917:Antibody Formation / Q000187:drug effects*; D001402:B-Lymphocytes / Q000187:drug effects / Q000276:immunology; D002470:Cell Survival / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D005260:Female; D007111:Immunity, Cellular / Q000187:drug effects*; D007376:Interleukin-2 / Q000096:biosynthesis; D015847:Interleukin-4 / Q000096:biosynthesis; D007694:Killer Cells, Natural / Q000187:drug effects / Q000276:immunology; D008213:Lymphocyte Activation / Q000187:drug effects; D051379:Mice; D008815:Mice, Inbred Strains; D010622:Phencyclidine / Q000633:toxicity*; D013154:Spleen / Q000166:cytology / Q000187:drug effects / Q000276:immunology; D013601:T-Lymphocytes / Q000187:drug effects / Q000276:immunology; D013602:T-Lymphocytes, Cytotoxic / Q000187:drug effects / Q000276:immunology; D006377:T-Lymphocytes, Helper-Inducer / Q000187:drug effects / Q000276:immunology / Q000378:metabolism
D007376:Interleukin-2; D015847:Interleukin-4; D010622:Phencyclidine