Nakane A, Minagawa T, Kato K
Department of Microbiology, Hokkaido University School of Medicine, Sapporo, Japan.
Infect Immun. 1988 Oct;56(10):2563-9. doi: 10.1128/iai.56.10.2563-2569.1988.
During a sublethal murine infection with Listeria monocytogenes cells, tumor necrosis factor (TNF) activity was detectable in neither sera nor spleen homogenates at any stage of the infection when a bioassay with L-929 cells (less than 4 U/ml) was used. However, injecting the mice with an immunoglobulin fraction obtained from a rabbit hyperimmunized with recombinant murine TNF-alpha resulted in acceleration of listeriosis. When 1 mg of anti-TNF antibody was injected per mouse, all the mice died from listeriosis, even though the infectious dose was sublethal for the untreated controls. The antigen-specific elimination of the bacterium from the spleens and livers of anti-TNF antibody-treated mice was delayed, depending on the dose of the antibody injected. Endogenous TNF seemed to be produced early in infection, because suppression of antilisterial resistance was significant when a single injection of anti-TNF antibody was given between day zero and day 2 of infection. The effect of endogenous TNF on antilisterial resistance was due to neither regulation of alpha interferon (IFN-alpha) and IFN-gamma production nor induction of IFN-beta subtype 1 (IFN-beta 1), because anti-TNF antibody treated-mice produced normal levels of IFN-alpha and IFN-gamma in the bloodstream during infection and administration of monoclonal anti-murine IFN-beta 1 antibody had no effect on the development of listeriosis. Alternatively, the listericidal activity of peritoneal macrophages of L. monocytogenes-infected mice could be abrogated by injection of anti-TNF antibody in vivo. These results suggest that the lower level of TNF is produced endogenously in mice that received L. monocytogenes infection and that it plays an essential role in the host defense against L. monocytogenes infection.
在用单核细胞增生李斯特菌细胞进行亚致死性小鼠感染期间，当使用L - 929细胞生物测定法（低于4 U/ml）时，在感染的任何阶段，血清和脾脏匀浆中均未检测到肿瘤坏死因子（TNF）活性。然而，给小鼠注射从用重组鼠TNF-α超免疫的兔获得的免疫球蛋白组分，可导致李斯特菌病加速发展。当每只小鼠注射1 mg抗TNF抗体时，所有小鼠均死于李斯特菌病，尽管感染剂量对未处理的对照小鼠是亚致死性的。抗TNF抗体处理的小鼠脾脏和肝脏中细菌的抗原特异性清除被延迟，这取决于注射的抗体剂量。内源性TNF似乎在感染早期产生，因为在感染的第0天至第2天之间单次注射抗TNF抗体时，抗李斯特菌抵抗力的抑制作用显著。内源性TNF对抗李斯特菌抵抗力的影响既不是由于α干扰素（IFN-α）和IFN-γ产生的调节，也不是由于IFN-β亚型1（IFN-β1）的诱导，因为抗TNF抗体处理的小鼠在感染期间血液中产生正常水平的IFN-α和IFN-γ，并且给予单克隆抗鼠IFN-β1抗体对李斯特菌病的发展没有影响。另外，体内注射抗TNF抗体可消除单核细胞增生李斯特菌感染小鼠腹膜巨噬细胞的杀菌活性。这些结果表明，感染单核细胞增生李斯特菌的小鼠内源性产生的TNF水平较低，并且它在宿主抵抗单核细胞增生李斯特菌感染的防御中起重要作用。
