Calderon Czarina, Rivera Luis, Hutchinson Paul, Dagher Hayat, Villanueva Elmer, Ghildyal Reena, Bardin Philip G, Freezer Nicholas J
Department of Respiratory and Sleep Medicine, Monash University and Medical Centre, Melbourne, Victoria, Australia.
Respirology. 2009 Mar;14(2):264-9. doi: 10.1111/j.1440-1843.2008.01464.x. Epub 2009 Jan 23.
Stable asthma is characterized by the production of Th2 cytokines, although Th1 cytokines may play a key role in aspects such as airway hyper-responsiveness. This study explored cytokine profiles associated with asthma exacerbation.
Intracellular T-cell cytokine production was measured in 16 children with acute severe asthma (emergency department), after convalescence (6 weeks, n = 13), with stable disease (after 6 months, n = 7) and in 14 age-matched hospital controls. Flow cytometry was used to identify CD4+ and CD8+ cells and to quantify intracellular T-cell production of the cytokines interferon (IFN)-gamma, IL-4 and IL-13. Cytokine production was compared using analysis of variance and random-effects generalized linear models and associations were examined using Pearson's correlation.
Cytokine production was evident in CD4+ and CD8+ cells, and compared with asthmatic children, non-asthmatics had a higher percentage of IFN-gamma+CD4+ cells (P = 0.01). The percentage of CD8+IFN-gamma+ cells was increased in the convalescent phase compared with acute (P = 0.009) and stable asthma (P = 0.004). IL-4+ cells were not significantly altered. IL-13 levels were higher in acute disease than in stable asthma (P = 0.009 in CD4+ cells) and IFN-gamma/IL-13 ratios indicated a Th2 profile during exacerbation (P = 0.005 in CD4+ cells).
IL-13, rather than IL-4, may play a pro-inflammatory role during acute severe asthma, whereas IFN-gamma responses were associated with recovery from acute severe asthma. These results suggest that altered T-cell cytokine profiles may contribute to the pathogenesis of and recovery from asthma exacerbations.
稳定期哮喘的特征是Th2细胞因子的产生,尽管Th1细胞因子可能在气道高反应性等方面起关键作用。本研究探讨了与哮喘急性发作相关的细胞因子谱。
对16例急性重症哮喘儿童(急诊科)、恢复期(6周,n = 13)、稳定期疾病(6个月后,n = 7)以及14例年龄匹配的医院对照者,检测其细胞内T细胞细胞因子的产生情况。采用流式细胞术鉴定CD4+和CD8+细胞,并定量细胞内T细胞产生的细胞因子干扰素(IFN)-γ、IL-4和IL-13。使用方差分析和随机效应广义线性模型比较细胞因子的产生情况,并使用Pearson相关性检验分析关联性。
CD4+和CD8+细胞中均有细胞因子产生,与哮喘儿童相比,非哮喘者IFN-γ+CD4+细胞的百分比更高(P = 0.01)。与急性期(P = 0.009)和稳定期哮喘(P = 0.004)相比,恢复期CD8+IFN-γ+细胞的百分比增加。IL-4+细胞无显著变化。急性疾病期的IL-13水平高于稳定期哮喘(CD4+细胞中P = 0.009),且IFN-γ/IL-13比值表明急性发作期呈Th2细胞因子谱(CD4+细胞中P = 0.005)。
在急性重症哮喘期间,IL-13而非IL-4可能起促炎作用,而IFN-γ反应与急性重症哮喘的恢复相关。这些结果表明,T细胞细胞因子谱的改变可能有助于哮喘急性发作的发病机制及恢复。