Rieckmann P, Weber F, Günther A, Martin S, Bitsch A, Broocks A, Kitze B, Weber T, Börner T, Poser S
Laboratory of Neurobiology, Department of Neurology, Georg-August-University Göttingen, Germany.
J Neuroimmunol. 1996 Feb;64(2):193-200. doi: 10.1016/0165-5728(95)00176-x.
The outcome of immune responses can be predicted by the lymphokine production pattern of the participating cells. Cytokines of the T helper type 1 (Th1) cells mediate inflammatory responses and delayed-type hypersensitivity (DTH), whereas Th2-like T cells predominantly produce cytokines, which stimulate antibody production by B cells. Immunoregulatory therapy of autoimmune diseases with unknown antigens may be achieved by inhibiting the production of inflammatory cytokines and induction of protective cytokines of Th2-like T cells. To determine the immunoregulatory capacity of the phosphodiesterase inhibitor pentoxifylline (PTX), which is known to suppress the production of tumor necrosis factor-alpha (TNF-alpha) and interferon-gamma (IFN-gamma), this drug was used in mitogen and antigen-stimulated lymphocyte cultures as well as in patients with multiple sclerosis. PTX significantly decreased TNF-alpha and interleukin-12 (IL-12), whereas it increased IL-4 and IL-10 production. In addition, PTX inhibited cell proliferation, which was associated with a marked reduction in CD25 (IL-2 receptor alpha-chain) and CD54 (intercellular adhesion molecule-1; ICAM-1) expression. Increasing doses of PTX significantly reduced TNF-alpha and IL-12 mRNA expression of blood mononuclear cells, but increased IL-4 and IL-10 expression in eight patients with relapsing-remitting multiple sclerosis. These results indicate that PTX modulates immune reactions favouring a Th2-like response and may therefore be useful for the treatment of autoimmune diseases with a dominant Th1-like T cell response.
免疫反应的结果可通过参与细胞的淋巴因子产生模式来预测。1型辅助性T细胞（Th1）产生的细胞因子介导炎症反应和迟发型超敏反应（DTH），而Th2样T细胞主要产生刺激B细胞产生抗体的细胞因子。对于抗原未知的自身免疫性疾病，可通过抑制炎性细胞因子的产生和诱导Th2样T细胞的保护性细胞因子来实现免疫调节治疗。为了确定磷酸二酯酶抑制剂己酮可可碱（PTX）的免疫调节能力（已知其可抑制肿瘤坏死因子-α（TNF-α）和干扰素-γ（IFN-γ）的产生），该药物被用于丝裂原和抗原刺激的淋巴细胞培养以及多发性硬化症患者。PTX显著降低了TNF-α和白细胞介素-12（IL-12），而增加了IL-4和IL-10的产生。此外，PTX抑制细胞增殖，这与CD25（IL-2受体α链）和CD54（细胞间黏附分子-1；ICAM-1）表达的显著降低有关。在8例复发缓解型多发性硬化症患者中，增加剂量的PTX显著降低了血液单核细胞中TNF-α和IL-12 mRNA的表达，但增加了IL-4和IL-10的表达。这些结果表明，PTX调节免疫反应，有利于Th2样反应，因此可能对以Th1样T细胞反应为主的自身免疫性疾病的治疗有用。
