Immunoregulation of transfusion-induced immunosuppression with inhibitors of the arachidonic acid metabolism.
To further define the role of arachidonic acid (AA) metabolites in transfusion-induced immunosuppression (TII), the effects of pharmacological manipulation of AA metabolism were examined in a rodent model. If the prostaglandins of the E series are mediators of TII, as has been recently hypothesized, then inhibition of cyclooxygenase (indomethacin) should abrogate whereas inhibition of lipoxygenase (nordihydroguaiaretic acid [NDGA]), or thromboxane synthetase (4-63557A) could potentiate the transfusion effect. Lewis rats received donor-specific transfusions from Buffalo rats in conjunction with one of the above inhibitors. Two weeks later they received intraabdominal Buffalo heart allografts or were used for one-way mixed lymphocyte reactions. Cyclooxygenase inhibition partially abrogated TII with shortened cardiac allograft survival. Lipoxygenase inhibition augmented TII, with depression of MLR and prolongation of allograft survival. Thromboxane synthetase inhibition had no effect. These results indicate that AA metabolites play a role in TII, and that immunoregulation via pharmacological manipulation of AA metabolism is possible.
Perez
R V
RV
Department of Surgery, University of Cincinnati Medical Center, Ohio 45267-0558.
Babcock
G F
GF
Alexander
J W
JW
D000276:Adjuvants, Immunologic / Q000494:pharmacology*; D000818:Animals; D016718:Arachidonic Acid; D001095:Arachidonic Acids / Q000037:antagonists & inhibitors* / Q000378:metabolism; D001782:Blood Donors; D001803:Blood Transfusion; D016861:Cyclooxygenase Inhibitors; D006085:Graft Survival; D007165:Immunosuppression Therapy; D016859:Lipoxygenase Inhibitors; D008297:Male; D051381:Rats; D011915:Rats, Inbred BUF; D011917:Rats, Inbred Lew; D013930:Thromboxane-A Synthase / Q000037:antagonists & inhibitors
D000276:Adjuvants, Immunologic; D001095:Arachidonic Acids; D016861:Cyclooxygenase Inhibitors; D016859:Lipoxygenase Inhibitors; D016718:Arachidonic Acid; D013930:Thromboxane-A Synthase