Leukotriene B4 and prostaglandin E2 mediate the inflammatory response of rabbit skin to intradermal arachidonic acid.
1. Acute inflammation was induced in rabbit skin by intradermal injection of arachidonic acid. 2. Inflammation was assessed by the local accumulation of intravenously-injected 125I-serum albumin (plasma extravasation) and histologically (polymorphonuclear leucocyte, PMNL infiltration). 3. Leukotriene B4 (LTB4) and prostaglandin E2 (PGE2) were extracted from skin and fractionated using C18 mini-columns. They were quantitated by specific radioimmunoassays and authenticated by reversed-phase high performance liquid chromatography analysis. 4. Maximally elevated levels of LTB4 and PGE2 were detected in skin 5 min after arachidonic acid injection. At subsequent times the eicosanoid content of the skin decreased. 5. The decrease in the eicosanoid content of the skin was due to rapid clearance (t 1/2 approximately 5 min) via the microvasculature and not a consequence of metabolism. 6. The concentration of LTB4 and PGE2 measured in inflamed skin was sufficient to account for the plasma extravasation and PMNL infiltration induced by arachidonic acid. The model therefore is useful for evaluating the anti-inflammatory efficacy of inhibitors of arachidonic acid metabolism including 5-lipoxygenase inhibitors. 7. The consequences of the rapid clearance of LTB4 from inflammatory sites are discussed with respect to its measurement in inflammatory disease and its role as an acute inflammatory mediator.
Aked
D M
DM
Imperial Chemical Industries PLC, Bioscience I Department, Macclesfield, Cheshire.
Foster
S J
SJ
D000818:Animals; D016718:Arachidonic Acid; D001095:Arachidonic Acids / Q000008:administration & dosage / Q000494:pharmacology*; D002465:Cell Movement; D002851:Chromatography, High Pressure Liquid; D015232:Dinoprostone; D005260:Female; D007249:Inflammation / Q000139:chemically induced / Q000378:metabolism / Q000503:physiopathology*; D007271:Injections, Intradermal; D007975:Leukotriene B4 / Q000378:metabolism / Q000502:physiology*; D009504:Neutrophils / Q000502:physiology; D011458:Prostaglandins E / Q000378:metabolism / Q000502:physiology*; D011817:Rabbits; D011863:Radioimmunoassay; D012711:Serum Albumin, Radio-Iodinated
D001095:Arachidonic Acids; D011458:Prostaglandins E; D012711:Serum Albumin, Radio-Iodinated; D007975:Leukotriene B4; D016718:Arachidonic Acid; D015232:Dinoprostone