Effects of recombinant human interleukin-2 and excipient infusion on plasma levels of prostaglandins and thromboxane B2 in sheep.
Systemic administration of recombinant human interleukin-2 (rIL-2) is used for treating some patients with advanced cancer. This therapy is limited by severe adverse reactions of cardiovascular and gastrointestinal origin. The effects of rIL-2 treatment on plasma levels of some prostanoids were examined in sheep in order to elucidate the mechanism of these adverse reactions. A total of 8 adult female Suffolk sheep were used. rIL-2 (0.1 mg/kg) was infused over a 30-min period in 4 sheep. Four different sheep in the control group received an excipient, which consisted of 5% mannitol and sodium dodecyl sulfate (SDS) (187 micrograms SDS/mg rIL-2), in the same way. Plasma levels of prostaglandin (PG) F2 alpha in rIL-2-treated animals showed significant increases from 1.5 to 6 h over the excipient treated animals with a maximal increase of 138% of the pooled zero time control value (p less than or equal to 0.01) at 6 h. The pooled zero time control plasma PGF2 alpha concentration was 443.0 +/- 45.9 pg/ml. Plasma levels of 6-keto-PGF1 alpha in rIL-2-treated animals showed a significant increase (p less than or equal to 0.02) over the excipient treated animals at 0.5 h but the value was only 103% of the pooled zero time control. Plasma levels of 6-keto-PGF1 alpha in excipient-treated animals showed a maximal increase of 156% of the pooled zero time control value (55.6 +/- 8.9 pg/ml) at 5 h and it was significantly higher than the rIL-2-treated sheep.(ABSTRACT TRUNCATED AT 250 WORDS)
O'Neill
C A
CA
Department of Veterinary Pharmacology and Toxicology, School of Veterinary Medicine, University of California, Davis 95616.
Gunther
R A
RA
Jesmok
G J
GJ
Giri
S N
SN
D015121:6-Ketoprostaglandin F1 alpha / Q000097:blood*; D000818:Animals; D015237:Dinoprost / Q000097:blood*; D005260:Female; D006801:Humans; D007262:Infusions, Intravenous; D007376:Interleukin-2 / Q000008:administration & dosage / Q000494:pharmacology*; D007700:Kinetics; D008353:Mannitol / Q000008:administration & dosage / Q000494:pharmacology*; D011994:Recombinant Proteins / Q000008:administration & dosage / Q000494:pharmacology; D012756:Sheep; D012967:Sodium Dodecyl Sulfate / Q000008:administration & dosage / Q000494:pharmacology*; D013929:Thromboxane B2 / Q000097:blood*; D013997:Time Factors
D007376:Interleukin-2; D011994:Recombinant Proteins; D012967:Sodium Dodecyl Sulfate; D008353:Mannitol; D013929:Thromboxane B2; D015121:6-Ketoprostaglandin F1 alpha; D015237:Dinoprost