Ulich T R, del Castillo J, Ni R X, Bikhazi N, Calvin L
Department of Pathology, University of California Irvine, School of Medicine 92717.
J Leukoc Biol. 1989 Feb;45(2):155-67. doi: 10.1002/jlb.45.2.155.
Tumor necrosis factor alpha (TNF) induces lymphopenia, neutropenia, and biphasic neutrophilia after intravenous injection of 3,000 U TNF in Lewis rats. The mechanism of TNF-induced lymphopenia was investigated by means of thoracic duct cannulation. Hourly measurements of lymphocyte recirculation via the thoracic duct failed to reveal any significant decrease in lymphocyte recirculation in TNF-treated vs. control rats, suggesting that a decrease in lymphocyte recirculation through the thoracic duct is not the mechanism for TNF-induced lymphopenia. The mechanism of TNF-induced neutropenia was investigated by administering TNF to rats in whom a neutrophilia had been induced with interleukin-1 (IL-1). In rats with neutrophilia, TNF resulted in a sharp decrease in the circulating neutrophil pool, demonstrating that TNF induces neutropenia by causing neutrophils to leave the circulating pool rather than decreasing neutrophil release from the marrow. The mechanism of neutropenia was furthermore shown to be due to the transient intravascular margination of neutrophils by administering epinephrine concomitantly with TNF. Epinephrine, which causes neutrophilia solely by demargination, abrogated the TNF-induced neutropenia and actually resulted in a neutrophilia that was greater than the neutrophilia occurring in epinephrine alone-treated rats, demonstrating both that TNF had already caused release of marrow neutrophils at the time of peripheral neutropenia, and that the paradoxical neutropenia was due to the transient intravascular margination of neutrophils. The known property of epinephrine to cause neutrophilia exclusively by demargination was proved by examination of the bone marrow of epinephrine-treated rats in whom no decrease in marrow neutrophils was observed (in contrast to TNF- and IL-1-treated rats in whom neutrophilia is accompanied by a depletion of marrow neutrophils). The mechanism of TNF-induced neutrophilia was investigated by modulating the magnitude of both the first and second peaks of neutrophilia by priming of rats with daily injections of IFN gamma for 2 days prior to administration of TNF. The first peak of neutrophilia in IFN gamma-primed TNF-treated rats was decreased in comparison to TNF alone-treated rats because of the well-known neutropenic and myelosuppressive effect of IFN gamma, which resulted in a decrease in the number of neutrophils that could be recruited to cause neutrophilia.(ABSTRACT TRUNCATED AT 400 WORDS)
肿瘤坏死因子α（TNF）在给Lewis大鼠静脉注射3000 U TNF后可诱导淋巴细胞减少、中性粒细胞减少和双相中性粒细胞增多。通过胸导管插管研究了TNF诱导淋巴细胞减少的机制。每小时对经胸导管的淋巴细胞再循环进行测量，结果显示与对照大鼠相比，经TNF处理的大鼠淋巴细胞再循环没有显著下降，这表明经胸导管的淋巴细胞再循环减少不是TNF诱导淋巴细胞减少的机制。通过给已用白细胞介素-1（IL-1）诱导中性粒细胞增多的大鼠注射TNF，研究了TNF诱导中性粒细胞减少的机制。在中性粒细胞增多的大鼠中，TNF导致循环中性粒细胞池急剧减少，表明TNF通过使中性粒细胞离开循环池而非减少骨髓中中性粒细胞的释放来诱导中性粒细胞减少。通过与TNF同时给予肾上腺素，进一步证明中性粒细胞减少的机制是由于中性粒细胞的短暂血管内边缘化。肾上腺素仅通过使边缘化的中性粒细胞游离而导致中性粒细胞增多，它消除了TNF诱导的中性粒细胞减少，实际上导致中性粒细胞增多，且比单独用肾上腺素处理的大鼠中出现的中性粒细胞增多更明显，这既表明在外周中性粒细胞减少时TNF已经导致骨髓中性粒细胞释放，也表明矛盾的中性粒细胞减少是由于中性粒细胞的短暂血管内边缘化。通过在给予TNF前2天每天给大鼠注射IFNγ进行预处理来调节中性粒细胞增多的第一峰和第二峰的幅度，研究了TNF诱导中性粒细胞增多的机制。与单独用TNF处理的大鼠相比，IFNγ预处理的TNF处理大鼠中性粒细胞增多的第一峰降低，这是因为IFNγ具有众所周知的中性粒细胞减少和骨髓抑制作用，导致可被募集以引起中性粒细胞增多的中性粒细胞数量减少。（摘要截短至400字）
