Lotz M, Seth P
Department of Medicine, University of California, San Diego, La Jolla 92093-0663.
Ann N Y Acad Sci. 1993 Jun 23;685:501-11. doi: 10.1111/j.1749-6632.1993.tb35912.x.
TGF beta is a cytokine which is involved with the regulation of different aspects of host defense responses to injury. Overexpression of TGF beta can lead to the conversion of its protective functions to pathogenetic manifestations. TGF beta is a potent factor in promoting anabolic aspects in connective tissue metabolism, and uncontrolled production of TGF beta has been associated with the development of fibrosis. With respect to its effects on immune and inflammatory responses, TGF beta is an important endogenous immunosuppressive factor which physiologically may protect the organism from tissue damage caused by chronic activation of leukocytes. As a result of overproduction in HIV infection, this function of TGF beta can contribute to noncytopathic mechanisms of immunodeficiency. TGF beta is involved with several aspects of HIV disease and promotes virus replication and spreading through multiple distinct mechanisms. It directly stimulates virus replication in infected monocytes and peripheral blood mononuclear cells under certain in vitro conditions. It may stimulate the production of other cytokines that enhance virus replication and it may be the mediator of other HIV-stimulating agents such as cocaine. It enhances recruitment of mononuclear phagocytes as cells susceptible to virus infection. Through its profound and broad inhibitory effects on different antiviral defense mechanisms, it facilitates more rapid progression of virus infection and increases susceptibility to opportunistic infections and malignancies. Although these findings are largely based on in vitro systems, the demonstration of TGF beta overexpression in HIV-infected patients supports the notion that this cytokine is an important pathogenetic mediator in HIV infection and its associated diseases. Therapeutic strategies to interfere with these functions of TGF beta are the development of TGF beta-neutralizing antibodies and soluble TGF beta-binding proteins and receptors as well as approaches directed at reducing TGF beta gene expression.
转化生长因子β（TGFβ）是一种细胞因子，参与宿主对损伤的防御反应不同方面的调节。TGFβ的过度表达可导致其保护功能转变为致病表现。TGFβ是促进结缔组织代谢合成方面的一个重要因素，TGFβ的失控产生与纤维化的发展有关。就其对免疫和炎症反应的影响而言，TGFβ是一种重要的内源性免疫抑制因子，在生理上可保护机体免受白细胞慢性激活所导致的组织损伤。由于在HIV感染中产生过多，TGFβ的这一功能可促成免疫缺陷的非细胞病变机制。TGFβ涉及HIV疾病的多个方面，并通过多种不同机制促进病毒复制和传播。在某些体外条件下，它可直接刺激受感染的单核细胞和外周血单核细胞中的病毒复制。它可能刺激其他增强病毒复制的细胞因子的产生，并且它可能是其他HIV刺激剂（如可卡因）的介质。它增强了作为易受病毒感染细胞的单核吞噬细胞的募集。通过其对不同抗病毒防御机制的深刻而广泛的抑制作用，它促进了病毒感染的更快进展，并增加了对机会性感染和恶性肿瘤的易感性。尽管这些发现主要基于体外系统，但在HIV感染患者中TGFβ过度表达的证明支持了这样一种观点，即这种细胞因子是HIV感染及其相关疾病中的一种重要致病介质。干扰TGFβ这些功能的治疗策略包括开发TGFβ中和抗体、可溶性TGFβ结合蛋白和受体，以及旨在降低TGFβ基因表达的方法。
