Smart Joanne M, Horak Elisabeth, Kemp Andrew S, Robertson Colin F, Tang Mimi L K
Department of Immunology, Royal Children's Hospital, Murdoch Children's Research Institute, Melbourne, Australia.
J Allergy Clin Immunol. 2002 Sep;110(3):450-6. doi: 10.1067/mai.2002.127283.
Atopic disease is associated with skewing of immune responses away from a T(H)1 toward a T(H)2 profile. Previous studies have implicated this cytokine imbalance in the development of disease. However, it is not known whether normalization of this imbalance is conversely associated with disease resolution.
To further delineate the role of reduced T(H)1 and increased T(H)2 cytokine production in the pathogenesis of atopic disease and to determine whether disease resolution is associated with alteration of cytokine profiles, we investigated cytokine responses in a cohort of adult patients with asthma followed from childhood.
A cohort of wheezy children and control subjects aged 7 to 10 years were recruited from 1964 to 1967. Subjects were reevaluated every 7 years to monitor the outcome of childhood asthma. At the 42-year follow-up, 89 subjects from this cohort were evaluated for mitogen and house dust mite (HDM)-induced T(H)1 (IFN-gamma) and T(H)2 (IL-4, IL-5, and IL-13) cytokine responses. Cytokine responses were compared in patients with ongoing asthma, patients with resolved asthma, and control subjects.
Patients with severe ongoing asthma had significantly reduced HDM-induced IFN-gamma production compared with that of control subjects and patients with resolved asthma. In contrast, HDM-induced IFN-gamma production in patients with resolved asthma was equivalent to that seen in control subjects. Patients with ongoing and resolved asthma produced significantly higher levels of IL-5 in response to HDM compared with that seen in control subjects, with levels being equivalent in patients with active and resolved asthma. HDM-induced IL-13 production was significantly increased in the patients with resolved asthma when compared with that seen in the control subjects. PHA-induced cytokine responses did not parallel HDM-induced responses.
Patients with persistent and severe atopic asthma have a reduced HDM-induced T(H)1 response, whereas those with resolved asthma do not. This suggests that reduced HDM-induced IFN-gamma production might be an important factor contributing to ongoing severe asthma and that normalization of allergen-induced T(H)1 responses might be important for disease resolution. The finding that all subjects with a history of asthma displayed increased HDM-induced T(H)2 (IL-5 and IL-13) cytokine responses, irrespective of the presence or absence of asthma, suggests that increased T(H)2 responses reflect the presence of the atopic state per se rather than being specifically linked to asthma.
特应性疾病与免疫反应从T(H)1型向T(H)2型偏移有关。既往研究认为这种细胞因子失衡与疾病发展有关。然而，尚不清楚这种失衡的正常化是否与疾病缓解相反相关。
为进一步阐明T(H)1减少和T(H)2细胞因子产生增加在特应性疾病发病机制中的作用，并确定疾病缓解是否与细胞因子谱改变相关，我们对一组自儿童期起就患有哮喘的成年患者的细胞因子反应进行了研究。
1964年至1967年招募了一组7至10岁的喘息儿童和对照受试者。每7年对受试者进行重新评估以监测儿童哮喘的转归。在42年随访时，对该队列中的89名受试者进行了丝裂原和屋尘螨（HDM）诱导的T(H)1（IFN-γ）和T(H)2（IL-4、IL-5和IL-13）细胞因子反应评估。比较了持续性哮喘患者、已缓解哮喘患者和对照受试者的细胞因子反应。
与对照受试者和已缓解哮喘患者相比，重度持续性哮喘患者HDM诱导的IFN-γ产生显著降低。相反，已缓解哮喘患者HDM诱导的IFN-γ产生与对照受试者相当。与对照受试者相比，持续性和已缓解哮喘患者对HDM刺激产生的IL-5水平显著更高，活动期和已缓解哮喘患者的水平相当。与对照受试者相比，已缓解哮喘患者HDM诱导的IL-13产生显著增加。PHA诱导的细胞因子反应与HDM诱导的反应不一致。
持续性和重度特应性哮喘患者HDM诱导的T(H)1反应降低，而已缓解哮喘患者则不然。这表明HDM诱导的IFN-γ产生减少可能是导致持续性重度哮喘的一个重要因素，且变应原诱导的T(H)1反应正常化可能对疾病缓解很重要。所有有哮喘病史的受试者无论是否存在哮喘，HDM诱导的T(H)2（IL-5和IL-13）细胞因子反应均增加，这一发现表明T(H)2反应增加反映了特应状态本身的存在，而非与哮喘有特异性关联。
