Xu B, Aoyama K, Kitani A, Yu S, Matsuyama T, Matsushita T
Department of Environmental Medicine, Faculty of Medicine, Kagoshima University, Japan.
J Interferon Cytokine Res. 1998 Jan;18(1):23-31. doi: 10.1089/jir.1998.18.23.
It has been proven that interleukin-12 (IL-12) can modify Th1 and Th2 cell-mediated immune diseases by altering the development and cytokine production of the cells. In this study, we investigated the in vivo immunomodulatory effect of recombinant murine IL-12 on contact hypersensitivity, a Th1 cell-mediated disease. For this purpose, Balb/C mice were sensitized with 3% 4-ethyoxymethylene-2-phenyl-oxazol-5-one (OXAZ), and recombinant mouse IL-12 was given simultaneously during the induction phase. Contact allergy was then elicited by ear challenge with 1% OXAZ. We examined the mouse ear swelling response, in vivo cytokine gene expression in the skin and local lymph nodes, and in vitro cytokine production by the spleen lymphocytes. It was found that in vivo IL-12 treatment during the induction phase significantly enhanced the ear swelling response to OXAZ in sensitized mice. Moreover, remarkable mononuclear cell infiltration and edema and higher expression of Th1 cytokine mRNAs (IL-2 and interferon-gamma) in the skin lesion and local lymph nodes were observed in contact allergic mice with IL-12 treatment compared with contact allergic mice without IL-12 treatment. The expression of Th2 cytokine mRNA (IL-4) in the skin lesion and local lymph nodes, however, was largely downregulated, with no change in IL-5 mRNA in IL-12-treated contact allergic mice. We found, unexpectedly, that, similar to the effects on phytohemagglutinin (PHA) stimulated in vitro IL-2 and IFN-gamma production, PHA-induced in vitro IL-4 production was enhanced in the spleen lymphocytes from IL-12-treated contact allergic mice. Our results indicate that exogenous IL-12 enhanced contact hypersensitivity probably because of the in vivo promoting and suppressing effects of IL-12 on Th1 and Th2 gene expression, respectively.
业已证明，白细胞介素-12（IL-12）可通过改变细胞的发育和细胞因子产生来调节Th1和Th2细胞介导的免疫疾病。在本研究中，我们调查了重组鼠IL-12对接触性超敏反应（一种Th1细胞介导的疾病）的体内免疫调节作用。为此，用3% 4-乙氧基亚甲基-2-苯基恶唑-5-酮（OXAZ）致敏Balb/C小鼠，并在诱导期同时给予重组小鼠IL-12。然后通过用1% OXAZ耳部激发来引发接触性过敏。我们检测了小鼠耳部肿胀反应、皮肤和局部淋巴结中体内细胞因子基因表达以及脾淋巴细胞的体外细胞因子产生。结果发现，在诱导期进行体内IL-12处理可显著增强致敏小鼠对OXAZ的耳部肿胀反应。此外，与未接受IL-12处理的接触性过敏小鼠相比，接受IL-12处理的接触性过敏小鼠的皮肤病变和局部淋巴结中观察到明显的单核细胞浸润和水肿以及Th1细胞因子mRNA（IL-2和干扰素-γ）的更高表达。然而，皮肤病变和局部淋巴结中Th2细胞因子mRNA（IL-4）的表达在很大程度上下调，接受IL-12处理的接触性过敏小鼠中IL-5 mRNA无变化。我们意外地发现，与对体外植物血凝素（PHA）刺激的IL-2和IFN-γ产生的影响类似，PHA诱导的体外IL-4产生在接受IL-12处理的接触性过敏小鼠的脾淋巴细胞中增强。我们的结果表明，外源性IL-12增强接触性超敏反应可能是因为IL-12分别对Th1和Th2基因表达具有体内促进和抑制作用。
