INVIVO EFFECTS OF NONSTEROIDAL ANTIINFLAMMATORY DRUGS ON RAT SKIN AND SYNOVIAL MAST CELL-INDUCED VASOPERMEABILITY

被引:16
作者
MALONE, DG
VIKINGSSON, A
SEEBRUCH, JS
VERBSKY, JW
DOLAN, PW
机构
[1] Section of Rheumatology, University of Wisconsin Department of Medicine, Madison
来源
ARTHRITIS AND RHEUMATISM | 1991年 / 34卷 / 02期
关键词
D O I
10.1002/art.1780340206
中图分类号
R5 [内科学];
学科分类号
1002 ; 100201 ;
摘要
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 H-1 and an H-2 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 H-1 and H-2 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 H-1 and H-2 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.
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页码:164 / 170
页数:7
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