Ayala A, Lehman D L, Herdon C D, Chaudry I H
Department of Surgery, Michigan State University, East Lansing.
Arch Surg. 1994 Nov;129(11):1172-8. doi: 10.1001/archsurg.1994.01420350070009.
To determine (1) whether interleukin-10 (IL-10) contributes to depressed T-cell responses observed following hemorrhage and (2) what effect other immunosuppressive agents known to play a role in hemorrhage have on IL-10 release.
Hemorrhage was induced in C3H/HeN mice. The mice were resuscitated and then killed 2 hours after hemorrhage to obtain plasma, splenocytes, splenic macrophages, and splenic T cells.
Decreased splenocyte/T-cell proliferation was associated with enhanced release of IL-10 by cells from hemorrhaged mice. However, unlike T cells, IL-10 release by macrophages was not comparatively elevated. While no changes were seen in systemic plasma levels of IL-10, the role of IL-10 as a localized immunosuppressant was demonstrated by the ability of IL-10 monoclonal antibody to restore T-cell proliferation following hemorrhage. Furthermore, elevated IL-10 release was prevented by the addition of ibuprofen or monoclonal antibody against transforming growth factor beta or IL-6. Since these agents have direct or indirect influences on prostanoid synthesis, studies were carried out examining the capacity of varying concentrations of prostaglandin E2 (PGE2) to augment IL-10 release by murine cloned Th2 cells (D10.G4.1) and by T cells from sham-operated or hemorrhaged mice. While the addition of PGE2, 10(-9) mol/L, potentiated the release of IL-10, this effect appears to be indirect, since the incorporation of monoclonal antibody to IL-4 prevented the release of IL-10 by PGE2-treated cells from sham-operated or hemorrhaged mice. Such a mechanism of eicosanoid-induced IL-4/IL-10 cell-mediated immunosuppression may directly contribute to the decreased capacity to ward off infectious challenge seen following hemorrhage.
确定（1）白细胞介素-10（IL-10）是否导致出血后观察到的T细胞反应受抑制，以及（2）已知在出血中起作用的其他免疫抑制剂对IL-10释放有何影响。
在C3H/HeN小鼠中诱导出血。对小鼠进行复苏，然后在出血后2小时处死以获取血浆、脾细胞、脾巨噬细胞和脾T细胞。
脾细胞/T细胞增殖减少与出血小鼠细胞IL-10释放增加有关。然而，与T细胞不同，巨噬细胞的IL-10释放没有相对升高。虽然IL-10的全身血浆水平未见变化，但IL-10单克隆抗体能够恢复出血后T细胞增殖，证明了IL-10作为局部免疫抑制剂的作用。此外，添加布洛芬或抗转化生长因子β或IL-6的单克隆抗体可防止IL-10释放增加。由于这些药物对前列腺素合成有直接或间接影响，因此进行了研究，检测不同浓度的前列腺素E2（PGE2）增强小鼠克隆Th2细胞（D10.G4.1）以及假手术或出血小鼠T细胞IL-10释放的能力。虽然添加10⁻⁹mol/L的PGE2可增强IL-10释放，但这种作用似乎是间接的，因为加入抗IL-4单克隆抗体可阻止假手术或出血小鼠经PGE2处理的细胞释放IL-10。类花生酸诱导的IL-4/IL-10细胞介导的免疫抑制机制可能直接导致出血后抵御感染能力下降。
