Regulation of eicosanoid production in rabbit colon by interleukin-1.
Prostaglandins and thromboxanes are increased in human and experimental colitis, but the factors that regulate this enhanced production are unclear. The present studies evaluate the effects of the monokines, interleukin-1 alpha and beta on eicosanoid production in rabbit colon. In tissue incubations the peak dose response of eicosanoid release to human recombinant interleukin-1 is 50 ng/ml. Interleukin-1 alpha increases prostaglandin E2 (PGE2) by 4.5 +/- 1.9 ng/g tissue, 6-keto PGF1 alpha by 6.2 +/- 2.7 ng/g, and thromboxane B2 by 2.1 +/- 0.3 ng/g compared to placebo. In isolated rabbit colons perfused with Krebs' solution, 10-h infusion of interleukin-1 alpha (50 ng/ml) progressively increases production of PGE2, 6-keto PGF1 alpha, and thromboxane B2. Bolus injections of bradykinin increase production of PGE2, but not 6-keto PGF1 alpha and thromboxane B2, and these responses are markedly augmented by interleukin-1 alpha: at 10 h bradykinin-stimulated PGE2 production is 518 +/- 104 vs. 95 +/- 18 ng/5 min (p less than 0.005), 6-keto PGF1 alpha is 172 +/- 88 vs. 8 +/- 2 ng/5 min (p less than 0.02), and thromboxane B2 is 60 +/- 14 vs. 13 +/- 4 ng/5 min (p less than 0.02) for interleukin-treated colons vs. placebo-treated colons, respectively. The response is greater with interleukin-1 alpha than interleukin-1 beta. This study demonstrates that interleukin-1 stimulates prostaglandin and thromboxane production in normal colon tissue. These data are consistent with the concept that interleukin-1 production by inflammatory cells may augment prostaglandin and thromboxane production in colitis.
Cominelli
F
F
Department of Medicine, Harbor-UCLA Medical Center, Torrance.
Nast
C C
CC
Dinarello
C A
CA
Gentilini
P
P
Zipser
R D
RD
D015121:6-Ketoprostaglandin F1 alpha / Q000096:biosynthesis; D000818:Animals; D001920:Bradykinin / Q000494:pharmacology; D003106:Colon / Q000378:metabolism*; D015232:Dinoprostone / Q000096:biosynthesis; D004347:Drug Interactions; D007375:Interleukin-1 / Q000502:physiology*; D011453:Prostaglandins / Q000096:biosynthesis*; D011817:Rabbits; D011994:Recombinant Proteins; D013929:Thromboxane B2 / Q000096:biosynthesis*
D007375:Interleukin-1; D011453:Prostaglandins; D011994:Recombinant Proteins; D013929:Thromboxane B2; D015121:6-Ketoprostaglandin F1 alpha; D015232:Dinoprostone; D001920:Bradykinin