T-2 toxin (T-2), produced by the genus Fusarium, is a cytotoxic trichothecene mycotoxin, a feed contaminant, and has been shown to be immunomodulatory. It is suspected that T-2-associated immunomodulation is mediated partly through the hypothalamic-pituitary-adrenal axis. The presence of endotoxin, a bacterial product capable of activating the hypothalamic-pituitary-adrenal axis as well as the levels of several hormones, also associated with activation of the hypothalamic-pituitary-adrenal axis, were determined in both vehicle- and toxin-treated animals. Endotoxemia was evident twenty-four hours after a single oral exposure to T-2. Blood levels of adrenocorticotropic hormone and corticosterone, parameters of the stress response, also increased twenty-four hours after T-2 exposure. Hypothalamic norepinephrine and serum corticosterone levels increased in a dose-related manner after two weeks of T-2 exposure. An increased corticosteroid level was associated with thymic involution leading potentially to decreased T-dependent antibody response, a known effect of T-2. The effects of exposure to T-2 on the development of both T-dependent and T-independent antibody response were determined in nonoperated, sham-operated and adrenalectomized mice. T-2 decreased the antibody response to a T-dependent antigen and increased a T-independent response. The effects of T-2 were partially nullified by adrenalectomy. These results provide a further confirmation of the postulate that the hypothalamic-pituitary-adrenal axis plays an important role in T-2 toxin-immunomodulation. In vitro studies were undertaken to investigate the direct effects of T-2 on various populations of lymphatic cells. Exposure to T-2 after twenty-four hours caused an increase in the uptake of 3H-thymidine by mouse splenic cells. Pokeweed mitogen stimulation also increased in this system; the response to lipopolysaccharide increased to a lesser extent. However, T-cell responses to phytohaemagglutinin and concanavalin A (Con A) decreased. Thymic cells were also sensitive to T-2. The possibility of pharmacological activity of T-2 with thymocytes was investigated. Both specific and nonspecific cell associations were observed. The association of T-2 with thymocytes was altered in the presence of dexamethasone, a synthetic corticosteroid. T-2 was shown to have both indirect as well as direct activities on the immune system. Endocrine dysfunction resulting from chronic stress and possible pharmacologic activity of T-2 provide the impetus for further investigations.
| Identifer | oai:union.ndltd.org:UTAHS/oai:digitalcommons.usu.edu:etd-4839 |
| Date | 01 May 1988 |
| Creators | Taylor, Michael Jay |
| Publisher | DigitalCommons@USU |
| Source Sets | Utah State University |
| Detected Language | English |
| Type | text |
| Format | application/pdf |
| Source | All Graduate Theses and Dissertations |
| Rights | Copyright for this work is held by the author. Transmission or reproduction of materials protected by copyright beyond that allowed by fair use requires the written permission of the copyright owners. Works not in the public domain cannot be commercially exploited without permission of the copyright owner. Responsibility for any use rests exclusively with the user. For more information contact Andrew Wesolek (andrew.wesolek@usu.edu). |
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