Gonzalo J A, González-García A, Kalland T, Hedlund G, Martínez C, Kroemer G
Centro de Biología Molecular (CSIC), Universidad Autónoma de Madrid, Spain.
Eur J Immunol. 1993 Sep;23(9):2372-4. doi: 10.1002/eji.1830230949.
Intravenous injections of 50 micrograms Staphylococcus aureus enterotoxin B (SEB) or bacterial lipopolysaccharide (LPS) are lethal, provided that mice are simultaneously sensitized with either N-galactosamine (GalN) or the anti-glucocorticoid RU-38486. Similar to the synthetic glucocorticoid (GC) receptor agonist dexamethasone, pharmacological doses of the immunomodulator linomide (quinoline-3-carboxamide) prevent death in all four models of lethal septic shock (LPS + GalN, LPS + RU-38486, SEB + GalN, and SEB + RU-38486) and inhibit the secretion of tumor necrosis factor, one of the major intermediate effector molecules of SEB and LPS toxicity. In this system, cyclosporine A (CsA), although effective in suppressing SEB toxicity, fails to counteract the lethal effect of LPS. This observation, together with the fact that linomide acts in the presence of excess amounts of GC receptor antagonist, indicates that linomide functions in a different way to that of known immunosuppressive agents like CsA and GC.
静脉注射50微克金黄色葡萄球菌肠毒素B（SEB）或细菌脂多糖（LPS）是致命的，前提是小鼠同时用N-半乳糖胺（GalN）或抗糖皮质激素RU-38486进行致敏。与合成糖皮质激素（GC）受体激动剂地塞米松类似，免疫调节剂利诺米德（喹啉-3-甲酰胺）的药理剂量可预防所有四种致死性脓毒症休克模型（LPS + GalN、LPS + RU-38486、SEB + GalN和SEB + RU-38486）中的死亡，并抑制肿瘤坏死因子的分泌，肿瘤坏死因子是SEB和LPS毒性的主要中间效应分子之一。在这个系统中，环孢素A（CsA）虽然能有效抑制SEB毒性，但无法抵消LPS的致死作用。这一观察结果，再加上利诺米德在存在过量GC受体拮抗剂的情况下仍能发挥作用，表明利诺米德的作用方式与已知的免疫抑制剂如CsA和GC不同。
