Prostaglandin formation in feline cerebral microvessels: effect of endotoxin and interleukin-1.
The pathogenesis of fever involves the appearance of interleukin-1 in the circulation in response to appropriate noxae (e.g., endotoxin) and subsequent generation of prostaglandin E2 in the CNS. The present study was undertaken to determine whether the cerebral microvasculature may function as a source of the fever-producing prostaglandin E2. Microvessels, consisting predominantly of capillaries, were isolated from the cat forebrain by selective sieving and glass bead elutriation. Preparations contained enzymes for the synthesis of 6-keto-prostaglandin F1 alpha (hence prostaglandin I2), prostaglandin E2, and possibly prostaglandin F2 alpha. No prostaglandin D2 was detected, nor was evidence obtained for the formation of 6-keto-prostaglandin E1. Intact microvessels released prostaglandin E2 and 6-keto-prostaglandin F1 alpha under basal conditions, the latter compound exceeding the former by about sevenfold. Endotoxin stimulated prostaglandin E2 release without significantly altering 6-keto-prostaglandin F1 alpha release. In contrast, monocyte-derived interleukin-1 reduced the release of both compounds, while recombinant interleukin-1 was ineffective. Endotoxin stimulation is likely directed on the cleavage of substrate arachidonic acid from precursor lipids, while inhibition from monocyte-derived interleukin-1 is ascribed to the presence of an interfering substance. This substance, like endotoxin, is thought to act prior to the cyclooxygenase cascade and its identity remains to be ascertained. We conclude that the cerebral microvasculature does not lend itself to an active role in the genesis of fever by being the site at which blood-borne interleukin-1 promotes prostaglandin E2 synthesis.(ABSTRACT TRUNCATED AT 250 WORDS)
D015121:6-Ketoprostaglandin F1 alpha / Q000378:metabolism; D000818:Animals; D001921:Brain / Q000098:blood supply* / Q000378:metabolism; D002196:Capillaries / Q000378:metabolism*; D002415:Cats; D015232:Dinoprostone; D004731:Endotoxins / Q000494:pharmacology*; D005260:Female; D066298:In Vitro Techniques; D007375:Interleukin-1 / Q000494:pharmacology*; D008297:Male; D011450:Prostaglandin Endoperoxides, Synthetic / Q000378:metabolism; D044262:Prostaglandin H2; D011453:Prostaglandins / Q000096:biosynthesis*; D011458:Prostaglandins E / Q000378:metabolism; D011463:Prostaglandins H / Q000378:metabolism; D011749:Pyrogens / Q000494:pharmacology
D004731:Endotoxins; D007375:Interleukin-1; D011450:Prostaglandin Endoperoxides, Synthetic; D011453:Prostaglandins; D011458:Prostaglandins E; D011463:Prostaglandins H; D011749:Pyrogens; D044262:Prostaglandin H2; D015121:6-Ketoprostaglandin F1 alpha; D015232:Dinoprostone