Tumor necrosis factor is a critical mediator in hapten induced irritant and contact hypersensitivity reactions.
Tumor necrosis factor is a critical mediator in hapten induced irritant and contact hypersensitivity reactions.
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DOI：
10.1084/jem.173.3.673
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发表时间：
1991-03-01
影响因子：
15.3
通讯作者：
Vassalli, P
中科院分区：
文献类型：
--
作者：
Piguet, P F;Grau, G E;Hauser, C;Vassalli, P
我们研究了细胞因子在非致敏和致敏小鼠对三硝基氯苯(TNCB)皮肤反应中的作用，即刺激性反应(IR)和接触性超敏反应(CH)。在激发前立即给予抗肿瘤坏死因子(TNF)抗体可消除CH的耳肿胀反应；针对干扰素γ的抗体或针对粒细胞/巨噬细胞集落刺激因子和白细胞介素3(IL-3)的抗体有部分抑制作用；抗IL-2受体抗体无作用。抗肿瘤坏死因子阻止了组织切片上可见的CH的各种特征，例如，真皮内的白细胞浸润和出血以及角质形成细胞的坏死。抗肿瘤坏死因子抗体也可预防胰岛素抵抗。在Northern blots中检测到了肿瘤坏死因子-α的表达，在未治疗的小鼠耳中可检测到肿瘤坏死因子-α的表达，在非致敏的小鼠中应用TNCB后检测到的表达增加，在致敏的小鼠中表达最高。用抗肿瘤坏死因子抗体处理后，肿瘤坏死因子mRNA的积聚在半抗原作用后0.5h即明显增加，持续时间长于72h，提示肿瘤坏死因子的产生具有自动扩增作用。用原位杂交的方法探讨了肿瘤坏死因子基因的细胞来源，基底层角质形成细胞的标记最强，但在真皮浸润液中也可检测到肿瘤坏死因子基因的表达。在对CH或IR敏感的部位(耳朵)或抵抗部位(足垫)应用半抗原(TNCB)后，观察到肿瘤坏死因子基因的积聚与炎症反应的强度密切相关。肿瘤坏死因子在CH和IR中的主要作用解释了这些反应在组织学上相似的方面，以及这些反应在不同解剖部位的极端变异性。
We examined the role of cytokines in the cutaneous response to the application of trinitrochlorobenzene (TNCB) in both nonsensitized and sensitized mice, i.e., in the irritant reaction (IR) and contact hypersensitivity reactions (CH). When administered immediately before challenge, anti-tumor necrosis factor (TNF) antibody abrogated the ear swelling response in CH; antibody directed against interferon gamma or antibodies to both granulocyte/macrophage colony-stimulating factor and interleukin 3 (IL-3) had a partial inhibitory effect; anti-IL-2 receptor antibody had no effect. Anti-TNF prevented the various features of the CH, as seen on histological sections, e.g., leukocyte infiltration and hemorrhages within the dermis and keratinocytes necrosis. Anti-TNF antibody also prevented the IR. The presence of TNF mRNA was evaluated on Northern blots; TNF-alpha mRNA was detectable in an untreated ear, increased after the application of TNCB in nonsensitized mice, and was highest in sensitized mice. TNF mRNA accumulation, which was evident 0.5 h after hapten application and lasted greater than 72 h, was abolished by treatment with anti-TNF antibody, thus suggesting an auto-amplification of TNF production. The cellular origin of TNF mRNA was explored by in situ hybridization; basal keratinocytes showed the highest labeling, but TNF mRNA was also detectable in cells of the dermal infiltrate. After hapten (TNCB) application at sites susceptible (the ear) or resistant (the foot pad) to CH or IR, a close correlation was observed between TNF mRNA accumulation and the intensity of the inflammatory reaction. The major role played by TNF in both the CH and the IR explains the histologically similar aspects of these reactions and the extreme variability of these reactions at various anatomical sites.