Szalay G, Ladel C H, Blum C, Kaufmann S H
Department of Immunology, University of Ulm, Germany.
J Immunol. 1996 Dec 1;157(11):4746-50.
Successful control of infectious disease depends on aquisition of an appropriate protective immune response. IFN-gamma, first produced by NK cells and then by Th1 cells, is central to acquired resistance against intracellular bacteria, including Listeria monocytogenes. In contrast, IL-4 is not generated to a measurable degree. Here we show that IL-4 is produced during listeriosis by IFN-gamma receptor gene disruption (IFN-gammaR(-/-)) mutant mice. Production of TNF was diminished, whereas IL-12 production was virtually unchanged in these mutants. Neutralization of IL-4 with anti-IL-4 mAb, as well as TNF-alpha reconstitution with rTNF-alpha, ameliorated listeriosis. These findings demonstrate the detrimental effects of IL-4 in listeriosis independent of IFN-gamma down-regulation and document the far-reaching consequences of a single cytokine deficiency on other cytokines. In cases where the primary gene defect cannot be restored, precise identification of secondary effects will promote rational immunotherapy based on neutralization or reconstitution of secondary immune deviations.
传染病的成功控制取决于获得适当的保护性免疫反应。干扰素-γ首先由自然杀伤细胞产生，然后由辅助性T细胞1（Th1）产生，对于获得性抵抗包括单核细胞增生李斯特菌在内的细胞内细菌至关重要。相比之下，白细胞介素-4（IL-4）的产生量未达到可测量的程度。在此我们表明，在李斯特菌病期间，干扰素-γ受体基因敲除（IFN-γR(-/-)）突变小鼠会产生IL-4。在这些突变体中，肿瘤坏死因子（TNF）的产生减少，而IL-12的产生基本未变。用抗IL-4单克隆抗体中和IL-4，以及用重组人TNF-α（rTNF-α）重建TNF-α，可改善李斯特菌病。这些发现证明了IL-4在李斯特菌病中的有害作用，且该作用独立于干扰素-γ的下调，并证明了单一细胞因子缺乏对其他细胞因子的深远影响。在原发性基因缺陷无法恢复的情况下，精确识别继发性效应将促进基于中和或重建继发性免疫偏差的合理免疫治疗。
