Leukotrienes, thromboxane, and platelet activating factor in organ transplantation

The antirejection eicosanoids--PGE2, (PGD2), and PGI2--have an attenuating effect on T-cell proliferation by inhibition of IL-1, IL-2, and class II antigen expression on macrophages, and the prorejection eicosanoids--TXA2, LTB4, LTC4, and LTD4--enhance T-cell proliferation. LTB4 stimulates IL-1 and IL-2 formation and expression of IL-2 receptor. The mechanism of enhancement of T-cell proliferation by TXA2 has not been demonstrated. LTC4 and LTD4 promote gamma-interferon release and can replace IL-2 as a stimulator of gamma-interferon. PAF at high concentrations inhibits lymphocyte proliferation. The eicosanoids interfere with the same mechanisms as CsA and corticosteroids on T-cell clonal expansion. In experimental organ transplantation, corticosteroids can be replaced by compounds preventing the formation or expression of the prorejection eicosanoids or analogs of antirejection eicosanoids as well as by PAF antagonists. In addition, these drugs exert synergistic effect with CsA and azathioprine.