Dearman R J, Warbrick E V, Skinner R, Kimber I
Syngenta Central Toxicology Laboratory, Alderley ParkMacclesfield, Cheshire SK10 4TJ, UK.
Food Chem Toxicol. 2002 Dec;40(12):1881-92. doi: 10.1016/s0278-6915(02)00179-5.
The cellular and molecular mechanisms that result in the induction of chemical respiratory sensitization are unclear, although there is evidence for the development of T helper (Th) 2 type responses and, in some cases, the production of IgE. We have compared cytokine secretion patterns stimulated by topical exposure of BALB/c strain mice or Brown Norway (BN) strain rats to the reference respiratory allergen trimellitic anhydride (TMA), or to the reference contact allergen 2,4-dinitrochlorobenzene (DNCB). Under conditions where TMA and DNCB provoke similar levels of immune activation [increases in lymph node cell (LNC) cellularity and proliferation] divergent cytokine expression patterns are elicited. TMA-activated LNC isolated from BALB/c mice or BN rats elaborated high levels of the Th2-type cytokines interleukin (IL)-10 and IL-13, but relatively little of the Th1-type cytokines IL-12 or interferon gamma. For LNC derived from both species there was a requirement for restimulation in vitro with the mitogen concanavalin A for IL-4 production. Generally, DNCB-stimulated LNC displayed the converse type 1 cytokine phenotype. The cytokine secretion profiles of LNC isolated from BN rats were considerably more variable than those observed for LNC from BALB/c mice. Statistically significant differences (P<0.01) between DNCB- and TMA-activated LNC were recorded for all cytokines in BALB/c strain mice. For the BN rat, differences reached statistical significance (P<0.01) only for the expression of IL-4 and IL-13. These data demonstrate that the intrinsic ability of DNCB and TMA to promote preferential Th1- and Th2-type responses, respectively, is species-independent and provide further evidence that chemical respiratory allergens are associated with polarized Th2-type responses. For the prospective assessment of chemical respiratory allergens as a function of induced cytokine secretion profiles, however, these data suggest that the use of the BALB/c strain mouse will provide the more robust method.
导致化学性呼吸道致敏的细胞和分子机制尚不清楚，尽管有证据表明会出现辅助性T细胞（Th）2型反应，并且在某些情况下会产生IgE。我们比较了将BALB/c品系小鼠或棕色挪威（BN）品系大鼠局部暴露于参考呼吸道变应原偏苯三酸酐（TMA）或参考接触性变应原2,4-二硝基氯苯（DNCB）后刺激产生的细胞因子分泌模式。在TMA和DNCB引发相似水平免疫激活的条件下（淋巴结细胞（LNC）细胞数量增加和增殖），会引发不同的细胞因子表达模式。从BALB/c小鼠或BN大鼠分离出的TMA激活的LNC产生高水平的Th2型细胞因子白细胞介素（IL）-10和IL-13，但Th1型细胞因子IL- 12或干扰素γ相对较少。对于来自这两个物种的LNC，需要用促细胞分裂剂刀豆球蛋白A在体外进行再刺激才能产生IL-4。一般来说，DNCB刺激的LNC表现出相反的1型细胞因子表型。从BN大鼠分离出的LNC的细胞因子分泌谱比从BALB/c小鼠分离出的LNC观察到的分泌谱变化大得多。在BALB/c品系小鼠中，DNCB激活的LNC和TMA激活的LNC之间所有细胞因子的差异均具有统计学意义（P<0.01）。对于BN大鼠，差异仅在IL-4和IL-13的表达上达到统计学意义（P<0.01）。这些数据表明，DNCB和TMA分别促进优先Th1型和Th2型反应的内在能力与物种无关，并进一步证明化学性呼吸道变应原与极化的Th2型反应有关。然而，对于根据诱导的细胞因子分泌谱对化学性呼吸道变应原进行前瞻性评估，这些数据表明使用BALB/c品系小鼠将提供更可靠 的方法。
