Abstract.
Objective: The purpose of this study was to assess the efficacy of topically applied ketoprofen lysine salt (KLS), a cyclooxygenase inhibitor, against the inflammatory changes induced by interleukin-1β (IL-1β) and bradykinin (BK) in hamster cheek pouch microcirculation. In addition, we characterised the pharmacological regulation of IL-1β activity in this model.¶Materials and methods: Male Syrian hamsters were used. Microcirculation was visualised by fluorescent microscopy. Leukocyte adhesion, permeability, perfused capillary length (PCL) and capillary red blood cell (RBC) velocity were evaluated.¶Treatments: KLS (25 μg/ml/min to 1.6 mg/ml/min) was topically applied for 3 min before topically administered IL-1β (1 μg/ml) and BK (10-4 M). Monoclonal anti-mouse IL-1β receptor antagonist (200 ng/ml), BK-B2 receptor antagonist (10-6 M), PAF inhibitor (10-5 M) and cycloheximide (10 mg/ml) were added topically 15, 10, 15 and 60 min, respectively, before IL-1β (1 μg/ml).¶Results: IL-1β caused a significant increase in microvascular permeability, a decrease in capillary RBC velocity followed by increased leukocyte adhesion in postcapillary venules. BK caused a marked increase in leukocyte adhesion and no decrease in PCL and RBC velocity. Treatment with KLS significantly inhibited both the leukocyte adhesion and microvascular leakage induced by the two mediators. The inflammatory effects induced by IL-1β were reduced by blockade of IL-1β receptors and by a BK-B2 receptor antagonist but were not affected by a PAF antagonist and protein synthesis inhibition.¶Conclusions: These results demonstrate that KLS is effective in preventing early inflammatory changes induced by both IL-1β and BK in the capillary network. Prostaglandin release and BK are essential components for IL-1β mediated responses, whereas neither PAF nor new protein synthesis appear to be linked to the early inflammatory changes induced by IL-1β.
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Received 12 September 2001; returned for revision 5 November 2001; accepted by M. J. Parnham 17 January 2002
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Daffonchio, L., Novellini, R. & Bertuglia, S. Protective effect of ketoprofen lysine salt on interleukin-1β and bradykinin induced inflammatory changes in hamster cheek pouch microcirculation. Inflamm. res. 51, 223–228 (2002). https://doi.org/10.1007/PL00000297
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DOI: https://doi.org/10.1007/PL00000297