Unilever R&D Bangalore, # 64 Main Road, Whitefield, Bangalore 560066, India.
J Autoimmun. 2013 Feb;40:9-20. doi: 10.1016/j.jaut.2012.07.004. Epub 2012 Aug 18.
Eosinophilia develops in reactive environment such as allergy, parasitic infections and in hypereosinophilic syndrome [HES]. Activated eosinophils are accompanied by a wide variety of inflammatory response due to release of toxic inflammatory mediators, which may result in severe tissue/organ damage at the site of eosinophilic infiltrations, due to degranulation. The factor responsible for the detrimental effect of activated circulatory eosinophils is an area less explored. In the present study, we determined the serum cytokine milieu of eosinophilic and control subjects, and also investigated the change in the pattern of cytokine released under mitogen stimulation. Increased level of various pro-inflammatory cytokines such as IL-1β, IL-6, TNF-α, IL-5 and IL-17 was detected in serum and culture supernatants of endotoxin stimulated white blood cells [WBCs] of eosinophilic subjects compared to control population. It was observed that endotoxin exposure in WBCs of eosinophilic subjects, led to increased release of IL-17, produced by TH17 subset of T-cell, contributing towards eosinophilic exuberations, in vitro. We observed non-specific lysis by eosinophils under such inflammatory milieu and synergistic eosinophilic activity in presence of IL-17 and IL-5 in combination. Taken together, our findings provide vital insight on TH17 lymphocyte mediated activation of eosinophils, via differential cytokine regulation, which play an important role in hypereosinophilic systemic inflammation.
嗜酸性粒细胞增多症发生在过敏、寄生虫感染和高嗜酸性粒细胞综合征[HES]等反应性环境中。由于释放有毒的炎症介质,激活的嗜酸性粒细胞伴随着各种各样的炎症反应,这可能导致嗜酸性粒细胞浸润部位的严重组织/器官损伤,由于脱颗粒。导致循环嗜酸性粒细胞激活产生有害影响的因素是一个研究较少的领域。在本研究中,我们确定了嗜酸性粒细胞和对照受试者的血清细胞因子环境,还研究了在有丝分裂原刺激下释放的细胞因子模式的变化。与对照组相比,在嗜酸性粒细胞的内毒素刺激的白细胞[WBC]的血清和培养上清液中检测到各种促炎细胞因子(如 IL-1β、IL-6、TNF-α、IL-5 和 IL-17)的水平升高。观察到嗜酸性粒细胞内毒素暴露导致 TH17 细胞亚群产生的 IL-17 释放增加,这有助于体外嗜酸性粒细胞增多。在这种炎症环境下,我们观察到嗜酸性粒细胞的非特异性溶解,并且在 IL-17 和 IL-5 联合存在时协同嗜酸性粒细胞活性。总之,我们的发现提供了关于 TH17 淋巴细胞通过差异细胞因子调节激活嗜酸性粒细胞的重要见解,这在高嗜酸性粒细胞性全身炎症中起着重要作用。