Asada H, Linton J, Katz S I
Dermatology Branch, National Cancer Institute, Bethesda, Maryland 20892-1908, U.S.A.
J Invest Dermatol. 1997 Apr;108(4):406-11. doi: 10.1111/1523-1747.ep12289700.
Recent studies have focused on characterizing the cytokine profile produced in the epidermis during the sensitization phase of contact sensitivity (CS). Some prior studies have also identified altered individual cytokine mRNA profiles in skin or draining lymph nodes (or several cytokine mRNA profiles in the epidermis) during the elicitation phase of CS. In this study we determined the dynamics of appearance of a battery of cytokine mRNA levels in both the epidermis and dermis during the elicitation phase of CS. We isolated mRNA from dispase-separated epidermis and dermis of TNCB-sensitized and naive BALB/c mice at various times after TNCB challenge. Changes in IFN-gamma and IL-4 mRNA levels (by semiquantitative RT-PCR) were more reproducible and dramatic than those of other cytokines studied (IL-1beta, IL-2, IL-10, and IL-12 p40). Compared to naive mice, sensitized mice had significantly elevated IL-4 mRNA signals 9 and 24 h (dermis), and 24 h (epidermis), after TNCB challenge. The increased IL-4 mRNA levels were mast-cell-independent, because sensitized mast-cell-deficient mice showed similar increases in IL-4 mRNA. To examine the role of endogenous IL-4 in CS elicitation, sensitized mice were treated with anti-IL-4 mAb 1 h before challenge. In accord with prior studies, anti-IL-4 mAb-pretreated mice showed increased ear swelling 24 h after challenge compared to mice pretreated with isotype control mAb. Anti-IL-4 mAb pretreatment also enhanced IFN-gamma, IL-2, IL-12 p40, and IL-1beta (but not IL-10) mRNA signals in the dermis of sensitized and challenged mice. These data indicate that IL-4 is produced in murine skin during the elicitation phase of CS and is an important down-modulator of inflammation. IL-4 may blunt CS by regulating local production of proinflammatory cytokines.
近期研究聚焦于表征接触性敏感（CS）致敏阶段表皮中产生的细胞因子谱。一些先前的研究还发现，在CS激发阶段，皮肤或引流淋巴结中个体细胞因子mRNA谱发生改变（或表皮中几种细胞因子mRNA谱发生改变）。在本研究中，我们确定了CS激发阶段表皮和真皮中一系列细胞因子mRNA水平出现的动态变化。我们在TNCB激发后的不同时间，从TNCB致敏和未致敏的BALB/c小鼠经dispase分离的表皮和真皮中分离mRNA。与所研究的其他细胞因子（IL-1β、IL-2、IL-10和IL-12 p40）相比，IFN-γ和IL-4 mRNA水平的变化（通过半定量RT-PCR）更具可重复性且更为显著。与未致敏小鼠相比，致敏小鼠在TNCB激发后9小时和24小时（真皮）以及24小时（表皮）时IL-4 mRNA信号显著升高。IL-4 mRNA水平的升高与肥大细胞无关，因为致敏的肥大细胞缺陷小鼠显示出类似的IL-4 mRNA升高。为了研究内源性IL-4在CS激发中的作用，在激发前1小时用抗IL-4单克隆抗体处理致敏小鼠。与先前的研究一致，与用同型对照单克隆抗体预处理的小鼠相比，抗IL-4单克隆抗体预处理的小鼠在激发后24小时耳部肿胀增加。抗IL-4单克隆抗体预处理还增强了致敏和激发小鼠真皮中IFN-γ、IL-2、IL-12 p40和IL-1β（但不包括IL-10）的mRNA信号。这些数据表明，IL-4在CS激发阶段在小鼠皮肤中产生，并且是炎症的重要下调调节因子。IL-4可能通过调节促炎细胞因子的局部产生来减轻CS。
