Chemotactic peptide stimulation of leukotrienes from healthy and inflamed rabbit colons

Prostaglandins, thromboxanes and leukotrienes are increased in human and experimental colitis. To evaluate the biosynthesis of these eicosanoids, colon inflammation was induced in rabbits by formalin enema followed by i.v. immune complexes, and the distal colon was perfused ex vivo. Bradykinin increased synthesis of prostaglandin E2 and thromboxane B2 more from colitis than from control colons (both P less than .001) but had no effect on leukotriene synthesis. The inflammatory cell agonist N-formylmethionyl-leucyl-phenylalanine (30 ng) also induced greater synthesis of prostaglandin E2 (70 +/- 13 vs. 14 +/- 6) and thromboxane B2 (84 +/- 22 vs. 20 +/- 11) from colitis than from control colons (P less than .01), but leukotriene B4 (416 +/- 68 vs. 438 +/- 128 ng/5 min) and leukotriene C4 (171 +/- 50 vs. 203 +/- 25 ng/5 min) synthesis were greatly augmented in both colitis and control colons. In vitro incubations demonstrated similar dose-dependent stimulation of leukotriene B4 by N-formylmethionyl-leucyl-phenylalanine in both colitis and control colons. These studies demonstrate that healthy colon tissue as well as colitis tissue can produce proinflammatory leukotrienes in response to bacterial peptides. Leukotriene production may contribute to the induction or mediation of colon inflammation.