Shahabi Shahram, Hassan Zuhair Muhammad, Jazani Nima Hosseini, Ebtekar Massoumeh
Department of Microbiology, Immunology and Genetics, Faculty of Medicine, Urmia University of Medical Sciences, Road of Nazloo, Urmia, Iran.
Med Hypotheses. 2006;67(4):900-3. doi: 10.1016/j.mehy.2006.03.039. Epub 2006 Jun 27.
T helper (Th) lymphocytes have been classified into distinct subsets, Th1 and Th2 on the basis of the cytokines they produce. According to the cross-regulatory properties of Th1 and Th2 cells, one would assume that to be affected by a Th1 type disease increases susceptibility to a Th1 type disease and inhibits a Th2 type disease and vice versa about being affected by a Th2 type disease. However, the pattern of related diseases does not necessarily follow the conventional pattern of inhibitory effects of Th1 and Th2 immune responses on each other. For example, Mycobacteria including BCG, that induce Th1 immune responses; can modulate some Th1 type autoimmune diseases including MS, experimental autoimmune encephalomyelitis (EAE; an animal model for Multiple Sclerosis) and insulin-dependent diabetes mellitus (IDDM) thereby leading to an alleviation of their symptoms. Also BCG precipitates a syndrome similar to systemic lupus erythematosus (SLE), a Th2 type disease; in NOD mice. The coexistence of the major Th2-mediated atopic diseases such as asthma, eczema and allergic rhinitis with the Th1-mediated autoimmune conditions including; coeliac disease (CD), IDDM, rheumatoid arthritis (RA) and psoriasis is another example that is in apparent disagreement with counter-regulatory effects of Th1/Th2 phenotypes.
SNS can be stimulated by pro-inflammatory cytokines, production of which is induced by mycobacteria including BCG. Although these cytokines can inhibit SNS activity in the site of inflammation and secondary lymphoid organs, they increase sympathetic tone in other places. Increased sympathetic tone can induce an anti-inflammatory and Th2 type milieu. This milieu can inhibit MS and IDDM and provide a susceptible environment for starting of SLE. Atopic diseases are Th2 type immune mediated diseases; therefore, they increase the production of Th2 type cytokine and decrease production of pro-inflammatory cytokines in the site of allergic reaction and also in secondary lymphoid organs. Therefore, atopic diseases decrease sympathetic tone in all tissues except in the sites of allergic reaction and secondary lymphoid organs. Decreased sympathetic tone results in a pro-inflammatory milieu and in such an environment, Th1 type autoimmune diseases can affect tissues.
辅助性T(Th)淋巴细胞已根据其产生的细胞因子被分为不同的亚群,即Th1和Th2。根据Th1和Th2细胞的交叉调节特性,人们会认为受Th1型疾病影响会增加对Th1型疾病的易感性,并抑制Th2型疾病,反之受Th2型疾病影响则相反。然而,相关疾病的模式并不一定遵循Th1和Th2免疫反应相互抑制作用的传统模式。例如,包括卡介苗在内的分枝杆菌可诱导Th1免疫反应,能调节一些Th1型自身免疫性疾病,包括多发性硬化症(MS)、实验性自身免疫性脑脊髓炎(EAE;多发性硬化症的动物模型)和胰岛素依赖型糖尿病(IDDM),从而减轻其症状。此外,卡介苗在非肥胖糖尿病(NOD)小鼠中引发一种类似于系统性红斑狼疮(SLE,一种Th2型疾病)的综合征。主要由Th2介导的特应性疾病如哮喘、湿疹和过敏性鼻炎与由Th1介导的自身免疫性疾病如乳糜泻(CD)、IDDM、类风湿性关节炎(RA)和牛皮癣并存,这是另一个明显与Th1/Th2表型的反调节作用不一致的例子。
促炎细胞因子可刺激交感神经系统(SNS),包括卡介苗在内的分枝杆菌可诱导这些细胞因子的产生。虽然这些细胞因子可在炎症部位和次级淋巴器官抑制SNS活性,但它们会增加其他部位的交感神经张力。交感神经张力增加可诱导抗炎和Th2型微环境。这种微环境可抑制MS和IDDM,并为SLE的发病提供易感环境。特应性疾病是Th2型免疫介导的疾病,因此,它们会增加Th2型细胞因子的产生,并减少过敏反应部位以及次级淋巴器官中促炎细胞因子的产生。因此,特应性疾病会降低除过敏反应部位和次级淋巴器官外所有组织的交感神经张力。交感神经张力降低会导致促炎微环境,在这样的环境中,Th1型自身免疫性疾病可影响组织。