Leukocyte recruitment in the subcutaneous sponge implant model of acute XXXX in the @entity35 is not mediated by leukotriene B1.

@entity32 @entity35278 @entity42430 @entity2605 @entity1421 @entity12032 @entity3365 @entity35 @entity3352 @entity3092 @entity8726
The subcutaneous sponge implant model of acute @entity32 in the @entity35 has been evaluated as a suitable test system for evaluating the potential anti-inflammatory efficacy of @entity12032 inhibitors. The inflammatory parameters measured were exudate volume and leukocyte recruitment. Specific radioimmunoassays were used to measure (1) @entity12032 ( @entity12032 ) and cyclo-oxygenase (CO) activity in exudate leukocytes stimulated ex vivo with @entity3365 , and (2) the LTB4 and @entity1421 content of inflammatory exudate. The NSAIDs @entity8726 and @entity3352 inhibited cell recruitment, exudate volume and CO activity with ED50S of approximately 1 mg per kg p.o. but failed to inhibit @entity12032 activity at 10 mg per kg p.o. Nafazatrom (Bayer 6575), @entity3092 and @entity2605 , which inhibit @entity12032 activity in vitro, were inactive against all parameters when dosed at 100 mg per kg p.o. The "mixed inhibitors" @entity35278 and @entity42430 were approximately equipotent inhibitors of @entity12032 activity but BW755C was 10 times more potent than @entity42430 against CO activity. BW755C was also greater than 10 times more potent at inhibiting cell recruitment and exudate volume than @entity42430 suggesting that the anti-inflammatory efficacy of the mixed inhibitors reflect their potency against CO rather than @entity12032 activity. Time course studies demonstrated that the inhibitor effects of BW755C and @entity42430 on leukocyte recruitment reflected a reduction in the PGE2 but not the LTB4 content of the inflammatory exudate. Polyester sponges soaked in high concentrations of LTB4 caused only a modest (2-fold) increase in leukocyte recruitment whilst physiological levels were inactive. The results taken together suggest that CO products make a major contribution to leukocyte recruitment in this model whilst the @entity12032 product LTB4 has little role. This model therefore is of little value for evaluating the anti-inflammatory efficacy of @entity12032 inhibitors. Moreover, the @entity35 would appear to be unsuitable for evaluating the role of LTB4 in acute @entity32 .
