Effect of lead, polychlorinated biphenyls, and cyclophosphamide on rat natural killer cells, interleukin 2, and antibody synthesis.
Interleukin 2 (IL2) activity, natural killer cell (NKC) cytotoxicity, and serum antibody (Ab) levels were assessed in rats exposed to 10 or 1000 ppm lead (Pb) as lead acetate in the drinking water or 50 or 500 ppm polychlorinated biphenyls (PCB) as Aroclor 1254 in the feed for 10 weeks or injected one time with 75 mg/kg cyclophosphamide (CY). Assays for IL2 activity and NKC cytotoxicity were also performed following in vitro exposure of rat splenocytes to Pb (0.4 or 40 micrograms/ml) or PCB (0.4 or 20.0 micrograms/ml) for 24 hr in vitro. NKC cytotoxicity and IL2 activity were significantly suppressed following in vitro exposure to either Pb or PCB. Chronic exposure to PCB, but not Pb, significantly reduced NKC cytolytic activity and significantly elevated Con A-stimulated IL2 activity. Ab synthesis was significantly suppressed in groups of rats chronically exposed to Pb or PCB. CY-injected rats had significantly reduced IL2 activity, NKC cytotoxicity, and Ab levels. High background levels of IL2, presumably induced by KLH injections shortly before termination, were significantly suppressed in PCB-, Pb-, and CY-treated rats. This suppression of IL2 activity was completely reversed by in vitro stimulation with Con A in Pb- or PCB-, but not CY-, treated groups. These results indicate that PCB, Pb, and CY alter IL2 synthesis and adversely affect NKC cytotoxicity and Ab synthesis following in vivo or in vitro exposure. The effects of PCB on NKC cytotoxicity may partially explain the tumor-promoting effect of this chemical via compromising immunosurveillance.
D000818:Animals; D000917:Antibody Formation / Q000187:drug effects; D003520:Cyclophosphamide / Q000633:toxicity*; D003602:Cytotoxicity, Immunologic / Q000187:drug effects; D006433:Hemocyanins / Q000276:immunology; D007074:Immunoglobulin G / Q000096:biosynthesis; D007376:Interleukin-2 / Q000096:biosynthesis*; D007694:Killer Cells, Natural / Q000187:drug effects*; D007854:Lead / Q000633:toxicity*; D008297:Male; D011078:Polychlorinated Biphenyls / Q000633:toxicity*; D051381:Rats; D011919:Rats, Inbred Strains; D013154:Spleen / Q000166:cytology
D007074:Immunoglobulin G; D007376:Interleukin-2; D007854:Lead; D003520:Cyclophosphamide; D006433:Hemocyanins; D011078:Polychlorinated Biphenyls; C032808:keyhole-limpet hemocyanin