Zhang X W, Hedlund G, Borgström P, Arfors K E, Thorlacius H
Department of Surgery, Malmö University Hospital, Lund University, Sweden.
J Leukoc Biol. 2000 Nov;68(5):621-6.
The immunomodulator Linomide (roquinimex) ameliorates the development of numerous inflammatory and immunological diseases, including sepsis, arthritis, and encephalomyelitis. However, the mechanism underlying this protective effect of Linomide remains unclear. In this study, we wanted to evaluate the effect of Linomide treatment on the different steps in the extravasation process of leukocytes stimulated by tumor necrosis factor alpha (TNF-alpha) in vivo. For this purpose, we used intravital microscopy in the mouse cremaster muscle microcirculation. We found that pretreatment with Linomide dose-dependently (3-300 mg/kg) reduced TNF-alpha-induced leukocyte adhesion and tissue recruitment. Notably, at 300 mg/kg response to TNF-alpha was nearly abolished, i.e. leukocyte adhesion was decreased by 83% and recruitment by 86%. In fact, the anti-inflammatory effect of this dose of Linomide corresponded in magnitude to the potency of 10 mg/kg of dexamethasone. Moreover, administration of Linomide did not alter the systemic leukocyte counts. On the other hand, 1-10 mg/kg of dexamethasone decreased the circulating number of mononuclear leukocytes by 77%. Taken together, our novel findings demonstrate that Linomide is a potent inhibitor of leukocyte adhesion and recruitment in cytokine-activated tissues. These data may help explain the documented protection provided by Linomide in inflammatory diseases characterized by cytokine and leukocyte accumulation.
免疫调节剂利索胺（罗喹美克）可改善多种炎症和免疫性疾病的发展，包括败血症、关节炎和脑脊髓炎。然而，利索胺这种保护作用的潜在机制仍不清楚。在本研究中，我们想评估利索胺治疗对体内肿瘤坏死因子α（TNF-α）刺激的白细胞渗出过程中不同步骤的影响。为此，我们在小鼠提睾肌微循环中使用了活体显微镜检查。我们发现，利索胺预处理（3-300mg/kg）剂量依赖性地降低了TNF-α诱导的白细胞黏附和组织募集。值得注意的是，在300mg/kg时，对TNF-α 的反应几乎完全消除，即白细胞黏附减少了83%，募集减少了86%。事实上，该剂量的利索胺的抗炎作用在强度上与10mg/kg地塞米松的效力相当。此外，给予利索胺并未改变全身白细胞计数。另一方面，1-10mg/kg的地塞米松使循环单核白细胞数量减少了77%。综上所述，我们的新发现表明，利索胺是细胞因子激活组织中白细胞黏附和募集的有效抑制剂。这些数据可能有助于解释利索胺在以细胞因子和白细胞积聚为特征的炎症性疾病中所提供的已记录的保护作用。
