Swierczyńska-Machura Dominika, Nowakowska-Świrta Ewa, Walusiak-Skorupa Jolanta, Piasecka-Zelga Joanna, Swiercz Radosław, Nocuń Marek, Pałczyński Cezary
Clinic of Allergology and Environmental Health .
J Immunotoxicol. 2014 Apr-Jun;11(2):166-71. doi: 10.3109/1547691X.2013.818745. Epub 2013 Aug 2.
Highly reactive, low-molecular-weight diisocyanates (DIC) are the most commonly identified cause of occupational asthma (OA). Animal/clinical studies of DIC asthma have been more limited compared with atopic asthma, and an understanding of DIC pathogenesis is less clear. The aim of this study was to investigate in a mouse model, toluene diisocyanate (TDI, as 2,4-TDI isomer)-induced inflammatory reactions/cytokine profile changes in the lungs and accompanying changes in lymph node lymphocyte sub-populations. The study used female BALB/cJ/Han/IMP mice that were exposed first intra-nasally and then in an inhalation chamber to TDI or air. After the final exposure, bronchoalveolar lavage fluid (BALF) was collected and changes induced in inflammatory cell composition, levels of key cytokines (i.e. IL-4, TNFα, IFNγ), and lymphocyte sub-population profiles within auricular lymph nodes, were evaluated. Total number of cells in the BALF of treated mice was significantly higher than in control mice BALF. There was also a significant increase in BALF neutrophil and eosinophil levels with TDI mice compared to in controls; lymphocyte and macrophage numbers did not significantly differ. A significant increase in BALF levels of TNFα and IFNγ was also noted in mice exposed to TDI relative to levels in controls. BALF IL-4 levels were also increased, but the change from control was not significant. Lastly, the levels/percentages of CD3(+)CD4(+) (T-helper [TH]) lymphocytes significantly increased in the lymph nodes of TDI-exposed groups while those of the CD3(+)CD8(+) cells decreased as compared to in control mice. These studies, the first to assess TDI-induced changes in levels of three key cytokines in BALF in conjunction with changes in local lymph nodes following first an intra-nasal and then a general inhalation exposure to a low-level of TDI, confirm that TDI inhalation induces a pathology manifested by airway inflammation, TH cell-derived cytokine production, and shifts in lymph node lymphocytes sub-populations toward increases in TH cells.
高反应性、低分子量二异氰酸酯（DIC）是职业性哮喘（OA）最常见的病因。与特应性哮喘相比，关于DIC哮喘的动物/临床研究较为有限，对DIC发病机制的了解也不太清楚。本研究的目的是在小鼠模型中研究甲苯二异氰酸酯（TDI，作为2,4 - TDI异构体）诱导的肺部炎症反应/细胞因子谱变化以及伴随的淋巴结淋巴细胞亚群变化。该研究使用雌性BALB/cJ/Han/IMP小鼠，先经鼻内暴露，然后在吸入舱中暴露于TDI或空气。末次暴露后，收集支气管肺泡灌洗液（BALF），评估炎症细胞组成、关键细胞因子（即IL - 4、TNFα、IFNγ）水平以及耳周淋巴结内淋巴细胞亚群谱的变化。处理组小鼠BALF中的细胞总数显著高于对照组小鼠的BALF。与对照组相比，TDI组小鼠BALF中的中性粒细胞和嗜酸性粒细胞水平也显著增加；淋巴细胞和巨噬细胞数量无显著差异。与对照组相比，暴露于TDI的小鼠BALF中TNFα和IFNγ水平也显著增加。BALF中IL - 4水平也有所增加，但与对照组相比变化不显著。最后，与对照小鼠相比，TDI暴露组淋巴结中CD3(+)CD4(+)（辅助性T细胞[TH]）淋巴细胞的水平/百分比显著增加，而CD3(+)CD8(+)细胞的水平/百分比则降低。这些研究首次评估了在低水平TDI经鼻内然后全身吸入暴露后，TDI诱导的BALF中三种关键细胞因子水平变化以及局部淋巴结变化，证实吸入TDI会引发一种以气道炎症、TH细胞衍生的细胞因子产生以及淋巴结淋巴细胞亚群向TH细胞增加方向转变为特征的病理状态。
