Eicosanoids and Elective Immunosuppression

  • P. W. Ramwell
  • M. L. Foegh
  • P. Kot


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.


Lymphocyte Proliferation Lipid Mediator Radiation Injury Foreign Antigen Arachidonic Acid Cascade 


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Copyright information

© Plenum Press, New York 1987

Authors and Affiliations

  • P. W. Ramwell
    • 1
    • 2
  • M. L. Foegh
    • 1
    • 2
  • P. Kot
    • 1
    • 2
  1. 1.Department of Physiology and BiophysicsGeorgetown University Medical CenterUSA
  2. 2.Department of Surgery Division of TransplantationWashingtonUSA

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