Daffonchio L, Novellini R, Bertuglia S
Dompé s.p.a., Medical Department, Milano, Italy.
Inflamm Res. 2002 May;51(5):223-8. doi: 10.1007/pl00000297.
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-1beta (IL-1beta) and bradykinin (BK) in hamster cheek pouch microcirculation. In addition, we characterised the pharmacological regulation of IL-1beta activity in this model.
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.
KLS (25 microg/ml/min to 1.6 mg/ml/min) was topically applied for 3 min before topically administered IL-1beta (1microg/ml) and BK (10(-4) M). Monoclonal anti-mouse IL-1beta receptor antagonist (200 ng/ml), BK-B2 receptor antagonist (10(-6) M), PAF inhibitor (10(-5) M) and cycloheximide (10 microg/ml) were added topically 15, 10, 15 and 60 min, respectively, before IL-1beta (1 microg/ml).
IL-1beta 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-1beta were reduced by blockade of IL-1beta receptors and by a BK-B2 receptor antagonist but were not affected by a PAF antagonist and protein synthesis inhibition.
These results demonstrate that KLS is effective in preventing early inflammatory changes induced by both IL-1beta and BK in the capillary network. Prostaglandin release and BK are essential components for IL-beta mediated responses, whereas neither PAF nor new protein synthesis appear to be linked to the early inflammatory changes induced by IL-1beta.
本研究旨在评估局部应用环氧化酶抑制剂酮洛芬赖氨酸盐（KLS）对白细胞介素-1β（IL-1β）和缓激肽（BK）诱导的仓鼠颊囊微循环炎症变化的疗效。此外，我们对该模型中IL-1β活性的药理调节进行了表征。
使用雄性叙利亚仓鼠。通过荧光显微镜观察微循环。评估白细胞黏附、通透性、灌注毛细血管长度（PCL）和毛细血管红细胞（RBC）速度。
在局部给予IL-1β（1μg/ml）和BK（10⁻⁴M）之前，局部应用KLS（25μg/ml/min至1.6mg/ml/min）3分钟。单克隆抗小鼠IL-1β受体拮抗剂（200ng/ml）、BK-B2受体拮抗剂（10⁻⁶M）、血小板活化因子（PAF）抑制剂（10⁻⁵M）和环己酰亚胺（10μg/ml）分别在给予IL-1β（1μg/ml）前15、10、15和60分钟局部添加。
IL-1β导致微血管通透性显著增加，毛细血管RBC速度降低，随后毛细血管后微静脉中的白细胞黏附增加。BK导致白细胞黏附显著增加，PCL和RBC速度无降低。KLS处理显著抑制了两种介质诱导的白细胞黏附和微血管渗漏。阻断IL-1β受体和BK-B2受体拮抗剂可降低IL-1β诱导的炎症效应，但不受PAF拮抗剂和蛋白质合成抑制的影响。
这些结果表明，KLS可有效预防IL-1β和BK在毛细血管网络中诱导的早期炎症变化。前列腺素释放和BK是IL-β介导反应的重要组成部分，而PAF和新蛋白质合成似乎均与IL-1β诱导的早期炎症变化无关。
