Effects of bromocriptine treatment on immune responses and 3-methylcholanthrene-induced tumorigenesis in rats.
Seven-week-old male Sprague-Dawley rats were given a single injection of 1.5 mg of 3-methylcholanthrene (3MC) to induce in situ fibrosarcomas. The rats were also treated with the dopamine agonist bromocriptine (BCR) from two days prior to 14 days after 3MC treatment and again for 14 consecutive days beginning at week 5. Tumor incidence was markedly increased and latency decreased in BCR-3MC rats compared to 3MC controls. Natural killer (NK) cell cytotoxicity responses and production of interleukin 2 (IL2) was enhanced at two weeks in rats treated with only BCR. Natural killer cell activity was suppressed at two weeks in rats treated with only 3MC. This effect was reversed by BCR treatment. Rats treated with 3MC and BCR had suppressed NK cell responses and production of IL2 and interferon-gamma (IFN) at 12 weeks. In another study, rats injected with 1, 3 or 5 mg/kg BCR for 14 consecutive days had increased NK cell activity and IL2 production at all doses and increased IFN production at the two high doses. Antibody (IgG) responses to an injected antigen and delayed-type hypersensitivity reactions were not affected by BCR treatment. Animals treated with the two high doses of BCR had decreased serum prolactin (PRL) levels. Serum growth hormone (GH) concentrations were markedly increased in the group treated with 3 mg/kg BCR. These data suggest that BCR enhances 3MC-induced tumorigenesis. The mechanism of this effect is apparently not mediated by suppression of the immune system since BCR-treated rats had selectively enhanced immune function. Enhancement of immune responses by BCR has not been previously reported.
Bussiere
J L
JL
Department of Microbiology and Immunology, School of Medicine, Temple University, Philadelphia, PA 19140.
Exon
J H
JH
Mather
G G
GG
D000818:Animals; D001971:Bromocriptine / Q000633:toxicity*; D003043:Cocarcinogenesis; D004357:Drug Synergism; D007107:Immune System / Q000187:drug effects*; D007166:Immunosuppressive Agents / Q000633:toxicity; D007371:Interferon-gamma / Q000096:biosynthesis; D007376:Interleukin-2 / Q000096:biosynthesis; D007694:Killer Cells, Natural / Q000187:drug effects / Q000276:immunology; D008297:Male; D008748:Methylcholanthrene / Q000633:toxicity; D009374:Neoplasms, Experimental / Q000139:chemically induced*; D051381:Rats; D011919:Rats, Inbred Strains
D007166:Immunosuppressive Agents; D007376:Interleukin-2; D001971:Bromocriptine; D008748:Methylcholanthrene; D007371:Interferon-gamma