Faculty Collaboration Database

In vivo effects of nonsteroidal antiinflammatory drugs on rat skin and synovial mast cell-induced vasopermeability. Arthritis Rheum 1991 Feb;34(2):164-70

Date

02/01/1991

Pubmed ID

1994913

DOI

10.1002/art.1780340206

Scopus ID

2-s2.0-0026084772 (requires institutional sign-in at Scopus site)   13 Citations

Abstract

Using our animal model of synovial mast cell-mediated arthritis in rats, we tested the effects of 3 nonsteroidal antiinflammatory drugs (NSAIDs) (aspirin, indomethacin, and ketoprofen) and an H1 and an H2 histamine receptor antagonist (diphenhydramine and cimetidine, respectively) on synovial and dermal mast cell-induced vasopermeability. Drug effects were assessed by quantifying the leakage of radiolabeled albumin into tissues following specific antigen-initiated activation of passively sensitized dermal and synovial mast cells. The 3 NSAIDs tested had different effects on synovial and dermal mast cell-induced vasopermeability. Aspirin and indomethacin significantly increased dermal and synovial plasma exudation (P less than or equal to 0.008). Ketoprofen decreased dermal (P = 0.015), but had no effect on synovial, vascular exudation. Complete histamine H1 and H2 receptor blockade with diphenhydramine and cimetidine, respectively, substantially decreased (P less than or equal to 0.0008), but did not completely inhibit, dermal and synovial mast cell-induced vasopermeability. However, the addition of indomethacin to the combined antihistamine regimen resulted in an increase in the leakage of the radiolabel into skin and synovium (back to control levels), despite the complete blockade of H1 and H2 receptors. Results of experiments with antihistamines and indomethacin suggest that mediators other than histamine are involved in synovial mast cell-induced inflammation. Furthermore, the differential response to ketoprofen indicates that the specific antigen-stimulated mediator release profiles of dermal and synovial mast cells are different. Our finding of enhanced synovial vascular leakage in animals treated with some NSAIDs, and no such effect by other NSAIDs, perhaps explains in part the diverse effects of these agents in humans with arthritis.

Author List

Malone DG, Vikingsson A, Seebruch JS, Verbsky JW, Dolan PW

Author

James Verbsky MD, PhD Professor in the Pediatrics department at Medical College of Wisconsin

MESH terms used to index this publication - Major topics in bold

Animals
Anti-Inflammatory Agents, Non-Steroidal
Aspirin
Capillary Permeability
Cimetidine
Diphenhydramine
Indomethacin
Ketoprofen
Male
Mast Cells
Rats
Rats, Inbred Strains
Skin
Synovial Membrane