Document Detail

Differences between rats and mice in the immunosuppressive activity of 2-methoxyethanol and 2-methoxyacetic acid.
MedLine Citation:
PMID:  1514188     Owner:  NLM     Status:  MEDLINE    
Previous studies from this laboratory have demonstrated that 2-methoxyethanol (ME) and its principal metabolite 2-methoxyacetic acid (MAA) are immunosuppressive in young adult male Fischer 344 rats. In the present study, the immunosuppressive potential of ME and MAA was evaluated in young adult female Fischer 344 rats and C57BL/6J mice. Rats and mice were dosed by gavage with either ME or MAA in water, at dosages ranging from 50-400 mg/kg/day, for 10 consecutive days. Rats and mice were examined for alterations in body, spleen and thymus weights and mitogen-induced proliferation of splenic lymphocytes in vitro; separate groups were employed for the antibody plaque-forming cell (PFC) response to trinitrophenyl-lipopolysaccharide (TNP-LPS). Rats dosed at 100-400 mg/kg/day ME and rats dosed at 50-400 mg/kg/day MAA had decreased thymus weights in the absence of decreased body or spleen weights. Lymphoproliferative (LP) responses to concanavalin A (Con A), phytohemagglutinin (PHA), pokeweed mitogen (PWM) and Salmonella typhimurium mitogen (STM) were all reduced in rats treated with all dosages of ME. Rats treated with MAA displayed similar reductions in these LP responses except that the responses to PWM and STM in rats dosed at 50 mg/kg/day were not reduced. In contrast to the effects of ME and MAA on these end points in the rat, no thymic involution or suppression of LP responses were observed in mice dosed at 50-400 mg/kg/day. The PFC response to TNP-LPS was suppressed in rats dosed with either ME or MAA at dosages of 100-400 mg/kg/day. ME and MAA, however, failed to suppress the PFC response in mice immunized with TNP-LPS. These results indicate that unlike Fischer 344 rats, C57BL/6J mice are insensitive to the immunosuppressive effects of ME and MAA at the dosages employed in this study. Whether the different sensitivities of these two rodent species to ME- and MAA-induced immunosuppression are due to immunologic, pharmacokinetic or metabolic differences within each species remains to be determined.
R J Smialowicz; M M Riddle; W C Williams; C B Copeland; R W Luebke; D L Andrews
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Publication Detail:
Type:  Comparative Study; Journal Article    
Journal Detail:
Title:  Toxicology     Volume:  74     ISSN:  0300-483X     ISO Abbreviation:  Toxicology     Publication Date:  1992 Aug 
Date Detail:
Created Date:  1992-09-29     Completed Date:  1992-09-29     Revised Date:  2006-11-15    
Medline Journal Info:
Nlm Unique ID:  0361055     Medline TA:  Toxicology     Country:  NETHERLANDS    
Other Details:
Languages:  eng     Pagination:  57-67     Citation Subset:  IM    
Health Effects Research Laboratory, U.S. Environmental Protection Agency, Research Triangle Park, NC 27711.
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MeSH Terms
Acetic Acids / toxicity*
Antibody Formation / drug effects
Body Weight / drug effects
Dose-Response Relationship, Drug
Ethylene Glycols / toxicity*
Immune Tolerance / drug effects
Lipopolysaccharides / administration & dosage
Lymphocyte Activation / drug effects
Mice, Inbred C57BL
Mitogens / pharmacology
Organ Size / drug effects
Rats, Inbred F344
Species Specificity
Spleen / anatomy & histology,  drug effects
Thymus Gland / anatomy & histology,  drug effects
Reg. No./Substance:
0/Acetic Acids; 0/Ethylene Glycols; 0/Lipopolysaccharides; 0/Mitogens; 0/trinitrophenyl-lipopolysaccharide; 109-86-4/methyl cellosolve; 625-45-6/methoxyacetic acid

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