Pharmacologic modulation of delayed-type hypersensitivity in mice.
In order to determine the mast cell requirements in murine delayed-type hypersensitivity (DTH), the effects of the antihistamine chlorpheniramine, the inhibitor of mast cell degranulation repirinast (CAS 73080-51-0, MY-5116), the lipoxygenase and cyclooxygenase inhibitor BW-755C (3-amino-1-[m-(trifluoromethyl)phenyl]-2-pyrazoline), and the cyclooxygenase inhibitors ibuprofen, diclofenac and phenylbutazone on murine DTH reactions were examined. When chlorpheniramine (50 mg/kg) was administered orally immediately after, 5 h, or 9 h after antigen challenge, it did not show any effect on sheep red blood cells (SRBC)-induced delayed footpad reaction (FPR) in mice. On the other hand, when chlorpheniramine was administered orally 16 h after antigen challenge, it significantly inhibited SRBC-induced delayed FPR (p < 0.01). When repirinast (30, 100 mg/ kg) was administered orally 16 h after antigen challenge, it significantly inhibited delayed FPR in a dose-dependent manner. BW-755C (50 mg/kg) showed no significant effect on delayed FPR when it was administered 1 h, 7 h, or 13 h after challenge. However, it significantly inhibited delayed FPR when it was administered 16 h after antigen challenge (p < 0.01). Ibuprofen, diclofenac, or phenylbutazone showed no significant effect on delayed FPR even if it was administered 16 h after antigen challenge. These results demonstrate that mast cells could be involved in DTH reactions and that histamine and leukotrienes may play an important role in DTH reactions in mice.
Yamada
N
N
Pharmaceuticals Laboratory, Yokohama Research Center, Mitsubishi Chemical Corporation, Japan.
Sugasawa
K
K
D000818:Animals; D015550:Cell Degranulation / Q000187:drug effects; D016861:Cyclooxygenase Inhibitors / Q000494:pharmacology; D004912:Erythrocytes / Q000276:immunology; D005528:Foot / Q000473:pathology; D006634:Histamine H1 Antagonists / Q000494:pharmacology; D006968:Hypersensitivity, Delayed / Q000188:drug therapy*; D016859:Lipoxygenase Inhibitors / Q000494:pharmacology; D008297:Male; D008407:Mast Cells / Q000187:drug effects; D051379:Mice; D008813:Mice, Inbred ICR; D012756:Sheep / Q000276:immunology
D016861:Cyclooxygenase Inhibitors; D006634:Histamine H1 Antagonists; D016859:Lipoxygenase Inhibitors