Role of prostaglandins in the behavioral changes induced by murine interleukin 1 alpha in the rat.
Continuous infusion of murine recombinant interleukin 1 alpha (rIL-1 alpha) produces weight loss, appetite suppression, reduction in horizontal locomotor activity (crossovers) and vertical locomotor activity (rears), and an increase in drinking behavior in the rat. The role of prostaglandins (PG) in the elicitation of these effects was studied. Infusion of rIL-1 alpha produced a transient increase in serum (PGs) which peaked at 24 to 48 h. This increase was completely inhibited by piroxicam. However, inhibition of circulating PG by piroxicam did not block the reductions in appetite, crossover, and rears induced by rIL-1 alpha; it restored normal drinking behavior and only partially restored body weight. Continuous intraperitoneal infusion of PGE2 at 24 micrograms/day exposed the animals to serum levels of PGE2 comparable to those produced by infusion with rIL-1 alpha. Yet, at the point of maximum weight loss induced by rIL-1 alpha (72 h), PGE2 infusion resulted in only a quarter of the weight loss. Compared with rIL-1 alpha, continuously infused PGE2 produced significantly smaller reductions in appetite, crossovers, and rears, and had no effect on drinking behavior. From these observations, we conclude that the rIL-1 alpha-induced increase in drinking behavior was fully dependent on products of the cyclooxygenase pathway, but not necessarily PGE2. However, because of the failure of piroxicam to fully reverse rIL-1 alpha effects on eating, mobility, and weight loss, there must also be a significant PG-independent component to account for the full range of rIL-1 alpha effects.
Otterness
I G
IG
Department of Immunology, Pfizer Inc., Groton, CT 06340.
Golden
H W
HW
Seymour
P A
PA
Eskra
J D
JD
Daumy
G O
GO
D000818:Animals; D000855:Anorexia / Q000139:chemically induced; D001522:Behavior, Animal / Q000187:drug effects* / Q000502:physiology; D001835:Body Weight / Q000187:drug effects; D015232:Dinoprostone / Q000097:blood / Q000494:pharmacology; D007263:Infusions, Parenteral; D007375:Interleukin-1 / Q000008:administration & dosage / Q000494:pharmacology*; D008297:Male; D010894:Piroxicam / Q000494:pharmacology; D011453:Prostaglandins / Q000502:physiology*; D051381:Rats; D011919:Rats, Inbred Strains
D007375:Interleukin-1; D011453:Prostaglandins; D010894:Piroxicam; D015232:Dinoprostone