Rosenblum M G, Donato N J
Department of Clinical Immunology and Biological Therapy, M.D. Anderson Hospital, Houston, Texas.
Crit Rev Immunol. 1989;9(1):21-44.
Homeostasis at the cellular level appears to be a complex state of equilibrium derived, in part, from multiple interactions among lymphokines, cytokines, growth factors, and hormones. Tumor necrosis factor (TNF-alpha) secreted by mitogen-stimulated macrophages and lymphotoxin (LT, TNF-beta) produced by mitogen-stimulated lymphocytes are two peptide hormones that share considerable homology in amino acid sequence and biological action. It has become increasingly evident that these factors, primarily involved in host defense, also mediate some responses to inflammatory, infectious, and neoplastic disease states. TNF-alpha is a low molecular weight (17,000-kdalton) peptide which seems to have a remarkably broad range of biological and immunologic effects, including antiviral action, growth regulation, and immunomodulation. These effects are shared by other lymphokines and cytokines such as interleukin 1 (IL-1), interferon alpha (IFN-alpha), interferon gamma (IFN-gamma), and TNF-beta. TNF-alpha also demonstrates both positive and negative cooperative growth-regulatory effects alone and in combination with antitumor drugs as well as with other bioactive peptides. Clinical trials are currently under way to determine the effectiveness of TNF-alpha as a single agent and in combination with biologic and chemotherapeutic agents against a variety of neoplastic diseases in man.
细胞水平的稳态似乎是一种复杂的平衡状态，部分源于淋巴因子、细胞因子、生长因子和激素之间的多种相互作用。有丝分裂原刺激的巨噬细胞分泌的肿瘤坏死因子（TNF-α）和有丝分裂原刺激的淋巴细胞产生的淋巴毒素（LT，TNF-β）是两种在氨基酸序列和生物学作用上具有相当同源性的肽类激素。越来越明显的是，这些主要参与宿主防御的因子也介导了对炎症、感染和肿瘤疾病状态的一些反应。TNF-α是一种低分子量（17,000道尔顿）的肽，似乎具有非常广泛的生物学和免疫学效应，包括抗病毒作用、生长调节和免疫调节。其他淋巴因子和细胞因子如白细胞介素1（IL-1）、α干扰素（IFN-α）、γ干扰素（IFN-γ）和TNF-β也具有这些效应。TNF-α单独以及与抗肿瘤药物和其他生物活性肽联合使用时，还表现出正负协同生长调节作用。目前正在进行临床试验，以确定TNF-α作为单一药物以及与生物制剂和化疗药物联合使用对人类各种肿瘤疾病的有效性。
