Relationship of the hypothalamic-pituitary-adrenal axis with chemically induced immunomodulation. I. Stress-like response after exposure to T-2 toxin.
T-2 toxin (T-2), a trichothecene mycotoxin, produced by several members of the genus Fusarium is a cytotoxic feed contaminant and has been shown to by immunomodulatory. It is suspected that T-2 associated immunomodulation is mediated partly through the hypothalamic-pituitary-adrenal (HPA) axis. T-2, prepared in 4% ethanol/corn oil, was administered orally to male CD-1 mice. Endotoxemia was evident 24 h after a single, oral exposure to T-2. Blood levels of corticosterone, indicative of the stress-response, increased 24 h after T-2 exposure. Hypothalamic norepinephrine and serum corticosterone levels increased in a dose-related manner after 2 weeks of T-2 exposure. Endotoxin, detected in the serum of animals exposed to 2.5 mg/kg T-2 for 1 week, was not associated with bacteremia. Neither endotoxin nor bacteremia were detectable after 2 or 4 weeks of T-2 exposure. Exposure to 2.5 mg/kg T-2 also affected several organs. The forestomach was ulcerated, with lymphocytic infiltration, epithelial proliferation, and hyperkeratinization. Increased spleen weight was associated with a proliferative red pulp. No histological changes were observed in the enlarged liver. Gastritis has been associated with increased corticosteroid production; cortical depletion and reduced mass of the thymus are phenomena attributable to increased corticosteroid levels. An increased corticosteroid level has been associated with thymic involution leading potentially to decreased T-dependent antibody response, a known effect of T-2.
Taylor
M J
MJ
Department of Animal, Dairy and Veterinary Sciences, Utah State University, Logan 84322-5600.
Smart
R A
RA
Sharma
R P
RP
D000276:Adjuvants, Immunologic / Q000633:toxicity*; D000311:Adrenal Glands / Q000187:drug effects; D000324:Adrenocorticotropic Hormone / Q000097:blood; D000818:Animals; D001835:Body Weight / Q000187:drug effects; D002395:Catecholamines / Q000378:metabolism; D003345:Corticosterone / Q000097:blood; D005753:Gastric Mucosa / Q000187:drug effects; D007030:Hypothalamo-Hypophyseal System / Q000187:drug effects* / Q000503:physiopathology; D008099:Liver / Q000187:drug effects; D051379:Mice; D009183:Mycotoxins / Q000097:blood; D009929:Organ Size / Q000187:drug effects; D010913:Pituitary-Adrenal System / Q000187:drug effects* / Q000503:physiopathology; D012717:Sesquiterpenes / Q000633:toxicity*; D013154:Spleen / Q000187:drug effects; D013312:Stress, Physiological / Q000139:chemically induced* / Q000503:physiopathology; D013605:T-2 Toxin / Q000633:toxicity*; D013950:Thymus Gland / Q000187:drug effects
D000276:Adjuvants, Immunologic; D002395:Catecholamines; D009183:Mycotoxins; D012717:Sesquiterpenes; D000324:Adrenocorticotropic Hormone; D013605:T-2 Toxin; D003345:Corticosterone