Immunotoxicity of bis(tri-n-butyltin)oxide in the rat: effects on thymus-dependent immunity and on nonspecific resistance following long-term exposure in young versus aged rats.
To investigate whether immune function suppression observed in an earlier study after short-term bis(tri-n-butyltin)oxide (TBTO) exposure also occurred after long-term treatment, function studies for specific and nonspecific resistance were performed after exposure of weaned male rats to diets containing 0, 0.5, 5, or 50 mg TBTO/kg for 4-6 and 15-17 months. Treatment for 4.5 months had no effect on body weight but reduced thymus weight at 50 mg/kg. Regarding the thymus-dependent immunity, delayed-type hypersensitivity reactions to ovalbumin and tuberculin were not depressed, in contrast to the results of the short-term study. The resistance to the nematode Trichinella spiralis was dose-relatedly suppressed at the 5 and 50 mg/kg levels, in both experiments (5.5 and 16.5 months exposure), as shown by increased counts of muscle larvae and depressed serum IgE titers. Also the inflammatory reaction around cysts in parasitized musculature was reduced. No significant reduction was found in IgM and IgG titers to T. spiralis, ovalbumin, and sheep red blood cells as determined by enzyme-linked immunosorbent assay. TBTO exposure at 50 mg/kg for 4.5 months significantly reduced thymus weight, but the response of thymocytes to T-cell mitogens was unaltered. TBTO treatment for 4.5 or 16 months did not influence the response of spleen cells to T-and B-cell mitogens and neither influenced spleen weight. A dose-related shift was observed in T- and B- cell numbers in mesenteric lymph nodes as shown by flow cytometry using monoclonal antibodies: treatment for 6 and 18 months reduced the relative count of T-lymphocytes and consequently increased the percentage of B-lymphocytes. As a result, the T:B ratio was reduced in the 5 and 50 mg/kg groups. Concerning the nonspecific resistance, TBTO exposure for 5 and 17 months reduced macrophage function at 50 mg/kg as shown by impaired splenic clearance of Listeria monocytogenes bacteria. Natural cell-mediated cytotoxicity of spleen and peritoneal cells was investigated in a 51Cr-release assay with YAC-lymphoma target cells. TBTO treatment significantly suppressed natural killer (NK) activity in spleen cells. Significant suppression was noted in all treatment groups following 16 months TBTO exposure; in contrast to treatment for 4.5 months. No significant alterations were observed in the spontaneous cytotoxicity of nonadherent and adherent peritoneal cells following 4.5 months treatment. Treatment of aged (i.e., 1-year-old) male rats for 5 months with the 50 mg/kg diet reduced thymus weight but had no effect on body or spleen weight.(ABSTRACT TRUNCATED AT 400 WORDS)
Vos
J G
JG
National Institute of Public Health and Environmental Protection, Bilthoven, The Netherlands.
De Klerk
A
A
Krajnc
E I
EI
Van Loveren
H
H
Rozing
J
J
D000375:Aging / Q000276:immunology*; D000818:Animals; D000917:Antibody Formation / Q000187:drug effects; D003602:Cytotoxicity, Immunologic / Q000187:drug effects; D006968:Hypersensitivity, Delayed / Q000276:immunology; D007109:Immunity / Q000187:drug effects*; D007113:Immunity, Innate / Q000187:drug effects; D007166:Immunosuppressive Agents / Q000633:toxicity*; D008089:Listeria monocytogenes / Q000276:immunology; D008214:Lymphocytes / Q000187:drug effects; D008297:Male; D011897:Random Allocation; D051381:Rats; D011919:Rats, Inbred Strains; D013154:Spleen / Q000187:drug effects; D013950:Thymus Gland / Q000187:drug effects; D013997:Time Factors; D014220:Trialkyltin Compounds / Q000633:toxicity*; D014235:Trichinellosis / Q000276:immunology
D007166:Immunosuppressive Agents; D014220:Trialkyltin Compounds; C005961:bis(tri-n-butyltin)oxide