Hosohara Katsushi, Ueda Haruyasu, Kashiwamura Shin-Ichiro, Yano Takako, Ogura Takeharu, Marukawa Seishiro, Okamura Haruki
Department of Emergency and Disaster Medicine, Hyogo College of Medicine, Nishinomiya, Hyogo 663-8501, Japan.
Clin Diagn Lab Immunol. 2002 Jul;9(4):777-83. doi: 10.1128/cdli.9.4.777-783.2002.
We investigated the acute hematological changes caused by interleukin-18 (IL-18) in mice. Intraperitoneal administration of IL-18 (2 microg/mouse) resulted in biphasic decreases in the number of leukocytes in the blood. The first phase of decrease occurred within 2 h of IL-18 administration and was followed by a transient increase at 5 h. The second phase of decrease occurred at around 6 h, reaching a nadir which lasted for more than 24 h. In mice deficient in inducible nitric oxide (NO) synthase, the first phase of reduction of leukocytes did not occur although the second phase of decrease was observed. In mice deficient in gamma interferon (IFN-gamma) or in mice depleted of natural killer cells and incapable of producing IFN-gamma, IL-18 had no effect on the number of circulating leukocytes. Levels of nitrite and/or nitrate in the serum were elevated within 2 h after administration of IL-18, reaching a peak at 4 h and then decreasing gradually to the basal level over a 24-h period of time. On the other hand, serum IFN-gamma levels changed in a biphasic manner, reaching a peak at 2 h after IL-18 administration, followed by a decrease in the basal level and a second increase at 6 h. Levels of IL-18 receptor mRNAs also showed biphasic changes in correlation with the changes in serum IFN-gamma levels. These results suggest that the changes in the leukocyte number following IL-18 administration are mediated by NO and IFN-gamma, with NO being involved in the first phase of reduction and IFN-gamma being involved in both phases.
我们研究了白细胞介素-18（IL-18）在小鼠体内引起的急性血液学变化。腹腔注射IL-18（2微克/小鼠）导致血液中白细胞数量出现双相下降。第一阶段的下降发生在注射IL-18后2小时内，随后在5小时出现短暂升高。第二阶段的下降发生在大约6小时，达到最低点并持续超过24小时。在诱导型一氧化氮（NO）合酶缺陷的小鼠中，虽然观察到白细胞数量下降的第二阶段，但白细胞减少的第一阶段未出现。在γ干扰素（IFN-γ）缺陷的小鼠或自然杀伤细胞耗竭且无法产生IFN-γ的小鼠中，IL-18对循环白细胞数量没有影响。注射IL-18后2小时内，血清中亚硝酸盐和/或硝酸盐水平升高，在4小时达到峰值，然后在24小时内逐渐降至基础水平。另一方面，血清IFN-γ水平呈双相变化，在注射IL-18后2小时达到峰值，随后降至基础水平以下，并在6小时再次升高。IL-18受体mRNA水平也与血清IFN-γ水平的变化相关呈双相变化。这些结果表明，注射IL-18后白细胞数量的变化由NO和IFN-γ介导，NO参与第一阶段的减少，IFN-γ参与两个阶段。
