The effects of continuous administration of murine interleukin-1 alpha in the rat.
Recombinant murine IL-1 alpha was administered continuously to rats by means of osmotic pumps implanted intraperitoneally. Continuous infusion of rIL-1 alpha in a range between 0.12 and 12.0 micrograms/day for four days was found to produce concentration-dependent weight loss. Behavioral parameters were continuously monitored and recorded at the 3.0 micrograms/day concentration in electronically-monitored activity cages during Days 2 through 5 of rIL-1 alpha administration. Parameters were separated into those affected during the dark phase (active period) or the light phase (resting period). Eating activity was found to be significantly reduced during each dark period through day 5, when compared with either untreated or PBS vehicle-infused animals. During the fourth and fifth days of infusion, however, eating behavior in animals infused with rIL-1 alpha began to increase toward control level in the latter, but not the earlier, half of the dark period. In contrast, drinking behavior was found to be significantly elevated only during the light periods. Continuous infusion of rIL-1 alpha also produced significant reductions in both horizontal locomotor activity (crossovers) and vertical locomotor activity (rears). However, in contrast to the trend toward a return of normal eating behavior, locomotor activity remained decreased through the fifth day of rIL-1 alpha infusion. These results suggest changes that could be produced by IL-1 in chronic inflammatory disease and infection.
Otterness
I G
IG
Department of Immunology, Drug Safety Evaluation and Molecular Genetics, Central Research Division, Pfizer, Inc., Groton, CT 06340.
Seymour
P A
PA
Golden
H W
HW
Reynolds
J A
JA
Daumy
G O
GO
D000818:Animals; D007263:Infusions, Parenteral; D007375:Interleukin-1 / Q000008:administration & dosage / Q000494:pharmacology*; D051381:Rats; D011994:Recombinant Proteins / Q000008:administration & dosage / Q000494:pharmacology
D007375:Interleukin-1; D011994:Recombinant Proteins