Sayers T J, Wiltrout T A, Bull C A, Denn A C, Pilaro A M, Lokesh B
Biological Carcinogenesis Development Program, NCI-FCRF, Frederick, MD 21701-1013.
J Immunol. 1988 Sep 1;141(5):1670-7.
The i.p. injection of mice with highly purified recombinant human rIL-1 alpha or beta resulted in the rapid influx of a large number of polymorphonuclear neutrophils (PMN) into the peritoneal cavity. Significant increases in the number of PMN were induced by doses of IL-1 which ranged from 0.005 to 5 ng/injection. Interestingly the dose response for PMN influx was bell-shaped because 50 ng of IL-1 did not result in a significant increase in peritoneal PMN. IL-1 induced PMN infiltration was detectable by 1 h with peak levels of PMN obtained by about 2 h, followed by a subsequent decline by 24 h. Other cytokines, IL-2, IFN-gamma, IFN alpha beta, granulocyte-CSF, granulocyte-macrophage-CSF, IL-3, TNF-alpha, and TNF-beta were compared to IL-1 for their ability to induce a PMN influx into the peritoneum. Only TNF-alpha or TNF-beta (lymphotoxin) were able to induce a significant influx of PMN within 2 h. However, based on total protein administered, about 100 times more TNF than IL-1 was required to produce a comparable PMN infiltration. Intraperitoneal injection of inhibitors of the cyclooxygenase or lipoxygenase pathways did not inhibit the IL-1-induced influx of PMN. Also, neither IL-1 nor TNF triggered an increase in PG or leukotriene release from peritoneal cells in vitro. Furthermore, direct peritoneal injection of leukotriene B4, a potent PMN chemoattractant in vitro, did not induce any significant increase in PMN in the peritoneal cavity indicating that chemotactic activity alone is insufficient for inducing peritoneal infiltration. These results suggest that the local production of very low levels of IL-1 in vivo would be sufficient to initiate a sequence of events that results in a rapid accumulation of PMN. Because IL-1 was not chemotactic for PMN in vitro, our data suggest that IL-1 induces production of factors that are chemotactic for PMN. Alternatively, IL-1 may act on other stages of the complex sequence of events that regulates the emigration of PMN into tissue sites in vivo. The synergy apparent in PMN influx when suboptimal concentrations of IL-1 and TNF were injected suggests that the local production of very low concentrations of these cytokines in situ could play a critical role in the emigration of PMN during infection.
给小鼠腹腔注射高度纯化的重组人rIL-1α或β，会导致大量多形核中性粒细胞（PMN）迅速流入腹腔。剂量为0.005至5 ng/注射的IL-1可诱导PMN数量显著增加。有趣的是，PMN流入的剂量反应呈钟形，因为50 ng的IL-1并未导致腹腔PMN显著增加。IL-1诱导的PMN浸润在1小时时可检测到，约2小时时达到PMN峰值水平，随后在24小时时下降。将其他细胞因子IL-2、IFN-γ、IFNαβ、粒细胞集落刺激因子（granulocyte-CSF）、粒细胞-巨噬细胞集落刺激因子（granulocyte-macrophage-CSF）、IL-3、肿瘤坏死因子-α（TNF-α）和肿瘤坏死因子-β（TNF-β）与IL-1比较，观察它们诱导PMN流入腹膜的能力。只有TNF-α或TNF-β（淋巴毒素）能够在2小时内诱导PMN显著流入。然而，基于所给予的总蛋白量，产生相当的PMN浸润所需的TNF比IL-1多约100倍。腹腔注射环氧化酶或脂氧化酶途径抑制剂不会抑制IL-1诱导的PMN流入。此外，IL-1和TNF在体外均未引发腹膜细胞释放PG或白三烯增加。此外，直接向腹膜注射白三烯B4（一种体外有效的PMN趋化剂）并未导致腹腔内PMN显著增加，这表明仅趋化活性不足以诱导腹膜浸润。这些结果表明，体内极低水平的IL-1局部产生足以启动一系列导致PMN快速积聚的事件。由于IL-1在体外对PMN无趋化作用，我们的数据表明IL-1诱导产生对PMN有趋化作用的因子。或者，IL-1可能作用于调节PMN体内迁移至组织部位的复杂事件序列的其他阶段。当注射次优浓度的IL-1和TNF时，PMN流入中明显的协同作用表明，这些细胞因子在体内原位极低浓度的局部产生可能在感染期间PMN迁移中起关键作用。
