Department of Pharmacology and Toxicology, Faculty of Veterinary Medicine, University of Warmia and Mazury, Oczapowskiego Street 13, 10-719 Olsztyn, Poland.
Int Immunopharmacol. 2017 Apr;45:98-109. doi: 10.1016/j.intimp.2017.02.005. Epub 2017 Feb 10.
To achieve a better understanding of mechanisms underlying the anti-asthmatic action of inhaled and systemic glucocorticoids (GCs) and to provide more data regarding the risk of a negative effect of inhaled GCs on CD4 T cells, a study was conducted on the effect of ciclesonide and methylprednisolone on CD4 effector (Teff), regulatory (Treg) and resting (Trest) T cells within respiratory and extra-respiratory tissues in a mouse model of allergic asthma. The study indicated that one, and possibly a key mechanism, underlying the anti-asthmatic action of inhaled and systemic GCs is the prevention of the activation and clonal expansion of CD4 Teff cells in the mediastinal lymph nodes (MLNs), which consequently prevents infiltration of the lungs with CD4 Teff cells. The beneficial effects of GCs in asthma treatment were not mediated through increased recruitment of Treg cells into the MLNs and lungs and/or local generation of Treg cells. The results demonstrated that inhaled and systemic GCs induced comparable depletion of normal CD4 Teff, Trest and Treg cells in the MLNs, head and neck lymph nodes and peripheral blood. Furthermore, inhaled, but not systemic GC therapy, led to the loss of these cells in the lungs. Thus, the study suggests that inhaled GC therapy may not be safer at all than systemic one with respect to the adverse effect on CD4 T cells present within and outside the respiratory tract. Moreover, administration of inhaled GCs can produce negative effects on lung-residing CD4 T cells.
为了更好地理解吸入性和全身性糖皮质激素（GCs）抗哮喘作用的机制，并提供更多关于吸入性 GCs 对 CD4 T 细胞产生负面影响的风险数据，在过敏性哮喘小鼠模型中，研究了环索奈德和甲泼尼龙对呼吸和呼吸外组织中 CD4 效应（Teff）、调节（Treg）和静止（Trest）T 细胞的影响。研究表明，吸入性和全身性 GCs 抗哮喘作用的一个（可能是关键）机制是预防纵隔淋巴结（MLNs）中 CD4 Teff 细胞的激活和克隆扩增，从而防止 CD4 Teff 细胞浸润肺部。GCs 在哮喘治疗中的有益作用不是通过增加 Treg 细胞募集到 MLNs 和肺部以及/或局部产生 Treg 细胞来介导的。结果表明，吸入性和全身性 GCs 在 MLNs、头颈部淋巴结和外周血中可引起正常 CD4 Teff、Trest 和 Treg 细胞的类似耗竭。此外，吸入性 GC 治疗而不是全身性 GC 治疗会导致这些细胞在肺部丢失。因此，该研究表明，吸入性 GC 治疗在呼吸道内外对 CD4 T 细胞的不良影响方面，可能并不比全身性 GC 治疗更安全。此外，吸入 GCs 的给药可能会对肺驻留的 CD4 T 细胞产生负面影响。
