Finkelman F D, Urban J F
University of Cincinnati College of Medicine, and the Cincinnati Veterans Administration Medical Center, Cincinnati, USA.
J Allergy Clin Immunol. 2001 May;107(5):772-80. doi: 10.1067/mai.2001.114989.
Although T(H)2 cytokine involvement in allergy makes these cytokines attractive therapeutic targets, they protect against ectoparasites and gastrointestinal worms and suppress inflammation induced by T(H)1 cytokines. T(H)2 cytokines induce mastocytosis, eosinophilia, IgE synthesis, and mucus production. Each element of this response protects against some worms; however, different worms are protected against by different elements of the total response. The induction of the entire response by most parasitic worms suggests that it is safer for the immune system to make a stereotyped worm-protective response than to attempt to match a more specific response to a particular worm. In contrast, the reciprocal antagonism between T(H)1 and T(H)2 cytokines suggests that it is safer for the immune system to limit immunopathology by suppressing inflammatory effector mechanisms not required for host protection against a particular pathogen class than to make an all-purpose inflammatory response. This, in turn, implies that innate immunity can distinguish different classes of parasites (eg, worms vs protozoa) but has limited ability to distinguish individual parasites within a class (eg, different worms). Although these considerations suggest that T(H)2 cytokine antagonists may increase the risk and severity of worm infections and T(H)1 cytokine-mediated inflammatory disorders, such therapy should be relatively safe if it is restricted to areas in which worm infections are rare and commonsense precautions are taken to minimize the risk of inducing T(H)1 cytokine-related inflammatory disease.
虽然辅助性T细胞2（T(H)2）细胞因子参与过敏反应使得这些细胞因子成为有吸引力的治疗靶点，但它们能抵御体外寄生虫和胃肠道蠕虫，并抑制由辅助性T细胞1（T(H)1）细胞因子诱导的炎症。T(H)2细胞因子可诱导肥大细胞增多、嗜酸性粒细胞增多、免疫球蛋白E（IgE）合成以及黏液分泌。这种反应的每个要素都能抵御某些蠕虫；然而，不同的蠕虫受到整个反应中不同要素的保护。大多数寄生蠕虫诱导整个反应，这表明免疫系统做出一种固定的蠕虫保护反应比试图针对特定蠕虫做出更特异性的反应更为安全。相比之下，T(H)1和T(H)2细胞因子之间的相互拮抗作用表明，免疫系统通过抑制宿主抵御特定病原体类别所需的炎症效应机制来限制免疫病理学，比做出一种通用的炎症反应更为安全。这反过来意味着先天免疫能够区分不同类别的寄生虫（例如，蠕虫与原生动物），但区分同一类别内个体寄生虫（例如，不同的蠕虫）的能力有限。尽管这些考虑因素表明T(H)2细胞因子拮抗剂可能会增加蠕虫感染的风险和严重程度以及T(H)1细胞因子介导的炎症性疾病，但如果将这种治疗限制在蠕虫感染罕见的地区，并采取常识性预防措施以尽量降低诱发T(H)1细胞因子相关炎症性疾病的风险，那么这种治疗应该相对安全。
