Early toxicity of recombinant interleukin-2 in cats.
Studies were conducted in cats to determine whether this species could serve as an animal model for the therapeutic toxicity of recombinant interleukin-2 in humans, and to establish the role of the area postrema in the causation of recombinant interleukin-2-induced vomiting. Injections of recombinant interleukin-2 (3.6 x 10(6) IU/kg, i.m.), given once every 24 hr for one to three days, evoked repeated vomiting in 4 out of 6 area postrema intact cats and in 3 out of 3 area postrema-ablated cats. These results suggest that the area postrema is not essential for the emetic action of recombinant interleukin-2. In anesthetized intact cats, no remarkable changes in ventilation, blood pressure, heart rate or blood pH were observed over 4.5 to 54 hr of continuous physiological recording after i.v. injections of recombinant interleukin-2 to a total dose as high as 27 x 10(6) IU/kg. Cat lymphocytes responded appropriately to the cytokinetic action of human recombinant interleukin-2.
Gonsalves
S F
SF
Department of Surgery, Dartmouth Medical School, Hanover, NH 03756.
Landgraf
B E
BE
Ciardelli
T L
TL
Borison
H L
HL
D000818:Animals; D001794:Blood Pressure / Q000187:drug effects; D002245:Carbon Dioxide / Q000097:blood; D002415:Cats; D002455:Cell Division / Q000187:drug effects; D002552:Cerebral Ventricles / Q000502:physiology; D004639:Emetics / Q000494:pharmacology; D005260:Female; D006339:Heart Rate / Q000187:drug effects; D006439:Hemodynamics / Q000187:drug effects; D006801:Humans; D007376:Interleukin-2 / Q000633:toxicity*; D008297:Male; D011994:Recombinant Proteins / Q000633:toxicity; D012119:Respiration / Q000187:drug effects; D013601:T-Lymphocytes / Q000187:drug effects; D013997:Time Factors
D004639:Emetics; D007376:Interleukin-2; D011994:Recombinant Proteins; D002245:Carbon Dioxide