Inhibition of the cutaneous response to antigen by a thromboxane-synthetase inhibitor (OKY-046) in allergic dogs.
We studied the effect of a selective thromboxane-synthetase inhibitor, sodium (E)-3-[4-(1-imidazolymethyl)-phenyl]-2-propanoate) (OKY-046) on the late-phase response to antigen in ragweed-sensitized dogs. Skin biopsies were performed before and 1, 6, and 24 hours after ragweed injection. OKY-046 was infused (100 micrograms.kg-1.min) from 1 hour before until 6 hours after intracutaneous ragweed in five dogs. The early clinical response to ragweed (wheal at 20 minutes) was not changed by OKY-046. A late-phase response (induration at 6 hours) was not observed in any of the OKY-046-treated dogs but was present at 6 hours in 4/5 dogs without OKY-046. Typical mast cells responded similarly in both groups with progressive degranulation during 24 hours. Maximal degranulation of atypical mast cells was delayed to 6 hours with OKY-046, whereas these cells responded completely at 1 hour without OKY-046. The inflammatory response to ragweed followed the same pattern in both groups, but the numbers of each cell type were decreased with OKY-046. With OKY-046, the cutaneous response to histamine was not changed significantly from baseline at 6 hours but was increased (p less than 0.05) at 24 hours, whereas without OKY-046, histamine response was significantly increased at 6 hours (p less than 0.001) and 24 hours (p less than 0.01). We conclude that OKY-046 alters the antigen-induced response of atypical mast cells, the subsequent cellular and clinical late-phase response, and prevents the increase in histamine response.
Cardiovascular Research Institute, University of California-San Francisco 94143-0130.
A B
AB
Becker
K F
KF
Chung
H
H
Aizawa
O L
OL
Frick
W M
WM
Gold
D000179:Acrylates / Q000627:therapeutic use*; D000818:Animals; D001491:Basophils / Q000187:drug effects / Q000276:immunology; D001706:Biopsy; D004285:Dogs; D004353:Drug Evaluation, Preclinical; D006632:Histamine / Q000031:analogs & derivatives / Q000494:pharmacology; D006967:Hypersensitivity / Q000188:drug therapy* / Q000276:immunology / Q000473:pathology; D008407:Mast Cells / Q000187:drug effects / Q000276:immunology; D008689:Methacrylates / Q000494:pharmacology / Q000627:therapeutic use*; D011058:Pollen / Q000276:immunology; D012867:Skin / Q000187:drug effects* / Q000276:immunology / Q000473:pathology; D012882:Skin Tests; D013930:Thromboxane-A Synthase / Q000037:antagonists & inhibitors*; D013997:Time Factors
D000179:Acrylates; D008689:Methacrylates; D006632:Histamine; D013930:Thromboxane-A Synthase; C034364:ozagrel; C027556:histamine phosphate