Eicosanoids and Elective Immunosuppression
The eicosanoids are the largest class of biologically active lipid mediators. They are believed to constitute one of the oldest and most ubiquitous of all the physiologic homeostatic mechanisms. An increasing number of plant products are being found to relate to eicosanoid synthesis and metabolism. Tissue dysfunction may readily occur following injury because the eicosanoids are not stored per se, but are rapidly released in large amounts for prolonged periods of time from the readily available long-chain polyenoic precursors. The pharmacological characterization of the eicosanoids permits the simplistic but useful division of the eicosanoids into “cytoprotective” and “pathogenic.” This has led to a pharmaceutical strategy of synthesizing stable analogs of the former and inhibitors and receptor antagonists of the latter. Such drugs facilitate the determination in different types of injury of the degree of involvement of the pathogenic mediators and also the therapeutic potential of the cytoprotective drugs. In general, the cytoprotective analogs are vasodilators, promote increase in cyclic adenosine monophosphate (AMP), enhance immunosuppression, and prolong allograft survival. In contrast, the pathogenic eicosanoids are vasoconstrictors and are associated with increased calcium input and lymphocyte proliferation. Some pathogenic mediators (e.g., platelet-activating factor, bradykinin) may act in part by activating acylhydrolases and thus promoting eicosanoid synthesis. However, other mediators do not, and therefore calcium entryblocking drugs may be more generally useful than eicosanoid synthase inhibitors and receptor antagonists.
KeywordsLymphocyte Proliferation Lipid Mediator Radiation Injury Foreign Antigen Arachidonic Acid Cascade
Unable to display preview. Download preview PDF.
- 2.Rouzer, C. A., and Samuelsson, B. 5-Lipoxygenase from human leukocytes associates with membrane in the presence of calcium. Adv. Prostaglandin Thromboxane Leukotriene Res. 17A: 60–63, 1987.Google Scholar
- 5.Robert, A. Prostaglandins and the digestive system. In: “The Prostaglandins,” Vol. 3. P. W. Ramwell, ed. Plenum Press, New York, 1977, pp. 225–266.Google Scholar
- 6.Foegh, M. L., Maddox, Y. T., Winchester, J., Rakowski T., Schreiner, G., and Ramwell, P. W. Adv. Prostaglandin Thromboxane Leukotriene Res. 12: 45–49, 1983.Google Scholar
- 7.Iacopino, V. J., Kot, P. A., and Ramwell, P. W. Systemic and pulmonary vascular effects of leukotrienes. In: “Prostaglandins and Cardiovascular Diseases.” T. Ozawa, K. Yamada, and S. Yamamoto, eds. Taylor & Francis Ltd, Philadelphia, 1986, pp. 203–211.Google Scholar
- 8.Braquet, P., Shen, T. Y., Touqui, L., and Vargaftig, B. B. Perspectives in platelet activity factor research. Pharmacol Rev., in press.Google Scholar
- 9.Foegh, M. L., Alijani, M. R., Helfrich, G. B., Khirabadi, B. S., Lim, K., and Ramwell, P. W. Elective immunosuppression. In: “Lipid Mediators in Immunology of Burn and Sepsis.” M. Paubert-Braquet and P. Braquet, eds. Plenum Press, London, in press.Google Scholar
- 10.Goodwin, J. S. Role of leukotriene B4 in T cell activation. Transplant. Proc. 18(Suppl4): 49–51, 1986.Google Scholar
- 11.Rola-Pleszczynski, M., and Gagnon, L. Natural killer cell function modulated by leukotriene B4: Mechanisms of action. Transplant. Proc. 18(Suppl 4): 44–48, 1986.Google Scholar
- 19.Rokash, J., and Fitzsimmons, B. Lipoxins—Do they have a biological role? Tranplant. Proc. 18(Suppl 4): 7–9, 1986.Google Scholar
- 21.Foegh, M. L., Hartmann, D.-P., Rowles, J. R., Khirabadi, B. S., Alijani, M. R., Helfrich, G. B., and Ramwell, P. W. Leukotrienes, thromboxane and platelet activating factor in organ transplantation. Adv. Prostaglandin Thromboxane Leukotriene Res. 17A: 140–146, 1987.Google Scholar