Kitani Hiroshi, Black Samuel J, Nakamura Yoshio, Naessens Jan, Murphy Noel B, Yokomizo Yuichi, Gibson John, Iraqi Fuad
Japan International Research Center for Agricultural Sciences, Tsukuba, Ibaraki, Japan.
Infect Immun. 2002 Apr;70(4):2210-4. doi: 10.1128/IAI.70.4.2210-2214.2002.
Mice whose tumor necrosis factor alpha (TNF-alpha) genes were disrupted developed higher levels of parasitemia than wild-type mice following infection with Trypanosoma congolense IL1180 or T. brucei brucei GUTat3.1, confirming the results of earlier studies. To determine whether TNF-alpha directly affects the growth of these and other bloodstream forms of African trypanosomes, we studied the effects of recombinant mouse, human, and bovine TNF-alpha on the growth of two isolates of T. congolense, IL1180 and IL3338, and two isolates of T. brucei brucei, GUTat3.1 and ILTat1.1, under axenic culture conditions. The preparations of recombinant TNF-alpha used were biologically active as determined by their capacity to kill L929 cells. Of five recombinant TNF-alpha lots tested, one lot of mouse TNF-alpha inhibited the growth of both isolates of T. brucei brucei and one lot of bovine TNF-alpha inhibited the growth of T. brucei brucei ILTat1.1 but only at very high concentrations and without causing detectable killing of the parasites. The other lots of mouse recombinant TNF-alpha, as well as human TNF-alpha, did not affect the growth of any of the test trypanosomes even at maximal concentrations that could be attained in the culture systems (3,000 to 15,000 U of TNF-alpha/ml of medium). These results suggest that exogenously added recombinant TNF-alpha generally does not inhibit the growth of African trypanosomes under the culture conditions we used. The impact of TNF-alpha on trypanosome parasitemia may be indirect, at least with respect to the four strains of trypanosomes reported here.
肿瘤坏死因子α（TNF-α）基因被破坏的小鼠在感染刚果锥虫IL1180或布氏布氏锥虫GUTat3.1后，其寄生虫血症水平高于野生型小鼠，这证实了早期研究的结果。为了确定TNF-α是否直接影响这些以及其他非洲锥虫血流形式的生长，我们在无菌培养条件下研究了重组小鼠、人及牛TNF-α对两种刚果锥虫分离株IL1180和IL3338以及两种布氏布氏锥虫分离株GUTat3.1和ILTat1.1生长的影响。所使用的重组TNF-α制剂具有生物活性，这通过它们杀死L929细胞的能力得以确定。在测试的五批重组TNF-α中，一批小鼠TNF-α抑制了两种布氏布氏锥虫分离株的生长，一批牛TNF-α抑制了布氏布氏锥虫ILTat1.1的生长，但仅在非常高的浓度下，且未导致可检测到的寄生虫死亡。其他批次的小鼠重组TNF-α以及人TNF-α，即使在培养系统中可达到的最大浓度（3000至15000 U的TNF-α/毫升培养基）下，也未影响任何测试锥虫的生长。这些结果表明，在我们使用的培养条件下，外源添加的重组TNF-α通常不会抑制非洲锥虫的生长。TNF-α对锥虫寄生虫血症的影响可能是间接的，至少就本文报道的四种锥虫菌株而言是这样。
