Shimizu Yasuo, Kuwabara Hidemasa, Ono Akihiro, Higuchi Seiichi, Hisada Takeshi, Dobashi Kunio, Utsugi Mitsuyoshi, Mita Yoshinori, Mori Masatomo
Numata National Hospital, Numata City, Gunma, Japan.
Immunopharmacol Immunotoxicol. 2006;28(2):295-304. doi: 10.1080/08923970600809389.
The balance between CD4(+) T helper (Th1) lymphocytes producing interferon-gamma or Interleukin-4 (Th2) in the lungs may vary among diseases and during the progression of interstitial pneumonia (IP). Both idiopathic pulmonary fibrosis (IPF) and collagen vascular diseases (CVD) are associated with IP, but the clinical course and the response to treatment are different. Since Th1 or Th2 modulating drugs have been proven to alter the lymphocyte balance in vitro, it is important to elucidate the Th1/Th2 profile in patients with active IP. Bronchoalveolar lavage (BAL) was performed in patients who had IPF (n = 12) or CVD (n = 12) with IP, as well as in patients who had bronchoectasis and bronchopneumonia (n = 12). The CVD patients had rheumatoid arthritis (n = 6), Sjogren's syndrome (n = 2), dermatomyositis (n = 1), progressive systemic sclerosis (n = 2), and CREST syndrome (n = 1) as the underlying diseases. IP activity was evaluated by measuring serum KL-6, which is a clinically useful indicator for IP. The Th1/ Th2 balance and the CD4(+)/CD8(+) ratio were determined for lymphocytes obtained from BAL by flow cytometric analysis. In IPF patients, the CD4(+)/CD8(+) ratio was lower than in CVD patients. IPF patients showed Th2 dominance and CVD patients showed Th1 dominance when IP was active as evaluated by the serum KL-6 level. These data indicated that the Th1/Th2 balance of CD4(+) T cells in the BAL differs between active IPF and CVD, even though KL-6 is elevated in both diseases. Therefore, the Th1/Th2 profile should be investigated to determine the use of Th1/Th2 modulator therapy for active IP with elevation of KL-6.
肺部产生干扰素-γ的CD4(+)辅助性T（Th1）淋巴细胞和产生白细胞介素-4的（Th2）淋巴细胞之间的平衡在不同疾病以及间质性肺炎（IP）进展过程中可能有所不同。特发性肺纤维化（IPF）和胶原血管疾病（CVD）均与IP相关，但临床病程和对治疗的反应有所不同。由于已证实Th1或Th2调节药物在体外可改变淋巴细胞平衡，因此阐明活动性IP患者的Th1/Th2特征很重要。对患有IPF（n = 12）或伴有IP的CVD（n = 12）的患者以及患有支气管扩张和支气管肺炎的患者（n = 12）进行了支气管肺泡灌洗（BAL）。CVD患者的基础疾病包括类风湿性关节炎（n = 6）、干燥综合征（n = 2）、皮肌炎（n = 1）、进行性系统性硬化症（n = 2）和CREST综合征（n = 1）。通过测量血清KL-6评估IP活动，血清KL-6是IP的一项临床有用指标。通过流式细胞术分析从BAL获得的淋巴细胞，确定Th1/Th2平衡和CD4(+)/CD8(+)比值。在IPF患者中，CD4(+)/CD8(+)比值低于CVD患者。根据血清KL-6水平评估，当IP处于活动期时，IPF患者表现为Th2优势，CVD患者表现为Th1优势。这些数据表明，尽管两种疾病中KL-6均升高，但活动性IPF和CVD患者BAL中CD4(+) T细胞的Th1/Th2平衡有所不同。因此，对于KL-6升高的活动性IP，应研究Th1/Th2特征以确定Th1/Th2调节剂疗法的使用。
