Fantuzzi G, Dinarello C A
Department of Medicine, University of Colorado Health Sciences Center, Denver 80262, USA.
Eur Cytokine Netw. 1998 Mar;9(1):85-92.
We have studied the responses of stem cell factor-deficient (SCF-) mice in two models of local inflammation, turpentine-induced tissue damage and zymosan-induced peritonitis. These mice have a profound mast cells deficiency. Following administration of either zymosan or turpentine, SCF- mice developed a more severe body weight loss than wild type (SCF+) mice. An exaggerated systemic production of interleukin-1beta (IL-1beta) and IL-6 was observed in SCF- mice. However, systemic tumor necrosis factor-alpha (TNF-alpha) levels were undetectable in SCF- mice following zymosan administration. The peritoneal lavage fluid (PLF) of SCF- mice also showed a marked increase in IL-1beta following zymosan administration, whereas local IL-6 and TNF-alpha production were not affected. In addition, PLF levels for the chemokine MIP-1alpha were strongly reduced in SCF- mice. This was associated with a reduced number of infiltrating cells. A possible mechanism for these differences was a reduction in IL-4 production in SCF- mice. Both local and systemic levels for IL-4 were significantly lower in SCF- mice following either zymosan or turpentine administration. Our results suggest that mast cells and/or SCF are important regulators of the production of cytokines in the course of inflammatory responses.
我们研究了干细胞因子缺陷（SCF-）小鼠在两种局部炎症模型中的反应，即松节油诱导的组织损伤和酵母聚糖诱导的腹膜炎。这些小鼠存在严重的肥大细胞缺陷。给予酵母聚糖或松节油后，SCF-小鼠比野生型（SCF+）小鼠体重减轻更严重。在SCF-小鼠中观察到白细胞介素-1β（IL-1β）和IL-6的全身产生过度。然而，给予酵母聚糖后，SCF-小鼠的全身肿瘤坏死因子-α（TNF-α）水平检测不到。SCF-小鼠的腹腔灌洗液（PLF）在给予酵母聚糖后IL-1β也显著增加，而局部IL-6和TNF-α的产生不受影响。此外，SCF-小鼠中趋化因子MIP-1α的PLF水平大幅降低。这与浸润细胞数量减少有关。这些差异的一个可能机制是SCF-小鼠中IL-4产生减少。给予酵母聚糖或松节油后，SCF-小鼠的局部和全身IL-4水平均显著降低。我们的结果表明，肥大细胞和/或SCF是炎症反应过程中细胞因子产生的重要调节因子。
