PHARMACOLOGICAL MODULATION OF DELAYED-TYPE HYPERSENSITIVITY IN MICE

In order to determine the mast cell requirements in murine delayed-typ e hypersensitivity (DTH). the effects of the antihistamine chlorphenir amine, the inhibitor of mast cell degranulation repirinast (CAS 73080- 51-0, MY-5116), the lipoxygenase and cyclooxygenase inhibitor BW-755C amino-1-[m-(trifluoromethyl)phenyl]-2-pyrazoline), and the cyclooxygen ase inhibitors ibuprofen diclofenac and phenylbutazone on murine DTH r eactions were examined. When chlorpheniramine (50 mg/kg) was administe red orally immediately after 5 h, or 9 h after antigen challenge, it d id not show any effect on sheep red blood cells (SRBC)-induced delayed footpad reaction (FPR) in mice. On the other hand, when chlorpheniram ine was administered orally 16 h after antigen challenge. it significa ntly inhibited SRBC-induced delayed FPR (p < 0.01). When repirinast (3 0, 100 mg/kg) was administered orally 16 h after antigen challenge, it significantly inhibited delayed FPR in a dose-dependent manner. BW-75 5C (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 significan tly 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 cou ld be involved in DTH reactions and that histamine and leukotrienes ma y play an important role in DTH reactions in mice.