ACTH Enhancement of T-Lymphocyte Cytotoxic Responses
- 92 Downloads
1. Corticotropin (ACTH) was one of the first neuropeptides shown to bind to receptors on leukocytes and modulate immune responses. Generally ACTH inhibits immune responses, but certain functions can be enhanced. The present study was performed to determine the effects of ACTH on cytotoxic T-lymphocyte responses, the components, and the major phenotypes of the participating cells.
2. The action of ACTH on cytotoxicity was measured in vitro, in assays utilizing T-lymphocytes that had been previously sensitized in vivo. The cells were then cultured with ACTH and target cells bearing the appropriate stimulatory major histocompatiblity antigens.
3. ACTH did not significantly affect a primary mixed lymphocyte reaction whereas it enhanced a secondary (memory) cytotoxic response up to 100% following 2 days of ACTH treatment. The effect was a shift in the kinetics of effector cell generation so that ACTH-treated cultures demonstrated an augmented cytotoxic activity on day 2, that was not as pronounced on day 3 as cytotoxic activity in control cultures became maximal. ACTH also inhibited Concanavalin A-stimulated T-lymphocyte mitogenesis. Immature thymocyte mitogenesis was inhibited more than that of mature thymocytes.
4. The finding that IFN-γ was elevated in the cultures suggested that ACTH may enhance memory cytotoxic responses through a combination of mechanisms such as direct cell alterations or synergy with regulatory cytokines. While corticosteroids are probably the most recognized neuroendocrine, stress hormone to affect immune functions, our study illustrates that other neuroendocrine factors such as ACTH, also directly affect immune functions.
Key Wordspsychoneuroimmunology stress immune system neuroendocrine system pituitary
Unable to display preview. Download preview PDF.
- Cohen, S., Tyrrell, D., and Smith, A. P. (1991). Psychological stress and susceptibility to the common cold. N. Engl. J. Med. 1991:606–612.Google Scholar
- Glaser, R., Kiecolt-Glaser, J. K., Bonneau, R. H., Malarkey, W. B., Kennedy, S., and Hughes, J. (1992). Stress-induced modulation of the immune response to recombinant hepatitis B vaccine. Psychom. Med. 54:22–29.Google Scholar
- Hartmeyer, M., Scholzen, T., Becher, E., Bhardwaj, R. S., Schwarz, T., and Luger, T.A. (1997). Human dermal microvascular endothelial cells express the melanocortin receptor type 1 and produce increased levels of IL-8 upon stimulation with alpha-melanocyte-stimulating hormone. J. Immunol. 159:1930–1937.PubMedGoogle Scholar
- Johnson, E. W. (1989) Distribution, modulation, and function of murine leukocyte adrenocorticotropin receptors: a dissertation, pp. 1–117. University of Texas Medical Branch, Galveston.Google Scholar
- Kavelaars, A., Ballieux, R. E., and Heijnen, C. (1988). Modulation of the immune response by proopiomelanocortin derived peptides. II. Influence of adrenocorticotropic hormone on the rise in intracellular free calcium concentration after T cell activation. Brain Behav. Immun. 2:57–66.CrossRefPubMedGoogle Scholar
- McEwen, B. S., Biron, C. A., Brunson, K. W., Bulloch, K., Chambers, W. H., Dhabhar, F. S., Goldfarb, R. H., Kitson, R. P., Miller, A. H., Spencer, R. L., and Weiss, J. M. (1997). The role of adrenocorticoids as modulators of immune function in health and disease: Neural, endocrine and immune interactions. Brain Res. Rev. 23:79–133.CrossRefPubMedGoogle Scholar
- Meyer, III, W. J., Smith, E. M., Richards, G. E., Cavallo, A., Morrill, A. C., and Blalock, J. E. (1987). In vivo immunoreactive adrenocorticotropin (ACTH) production by human mononuclear leukocytes from normal and ACTH-deficient individuals. J. Clin. Endocrinol. Metabol 64:98–105.Google Scholar
- Mishell, B. B., and Shiigi, S. M. (1980) Selected Methods in Cellular Immunol. pp. 1–486. W. H. Freeman, San Francisco.Google Scholar
- Smith, E. M. (1994). Corticotropin and Immunoregulation.in by Scharrer, B E., Smith, M., and Stefano, G. B. (eds), Neuropeptides and Immunoregulation. Springer-Verlag, Berlin, pp. 28–45.Google Scholar
- Smith, E. M., Hughes, T. K., Jr., Hashemi, F., and Stefano, G. B. (1992). Immunosuppressive effects of corticotropin and melanotropin and their possible significance in human immunodeficiency virus infection. Proc Natl Aca Sci USA 89:782–786.Google Scholar