Gemmell C G
Department of Bacteriology, University of Glasgow Medical School, Royal Infirmary, UK.
J Antimicrob Chemother. 1993 Feb;31 Suppl B:23-33. doi: 10.1093/jac/31.suppl_b.23.
The advent of cytokines as possible therapeutic agents has stimulated investigation of old and new antibiotics for their potential activity as immunomodulators over and above their primary bactericidal or bacteristatic activity. Such investigations have focused largely on in-vitro functions of peripheral blood cells such as polymorphonuclear leucocytes and monocytes. Graded doses of various antibiotics have been tested for their ability to affect functions such as chemotaxis, phagocytic ingestion and killing, as well as particular biochemical mechanisms, such as a generation of superoxide. These drugs have been shown to have no effect on host defences (beta-lactams), or depress immune function (tetracyclines and teicoplanin), or display synergy with the immune system (macrolides and quinolones), or enhance immune function (certain cephalosporins). In several instances, biological activity has been demonstrated at drug concentrations outside the therapeutic range. In addition, it has been recognized that a number of drugs can be concentrated within the phagocytic cells and, by so doing, are transported to the site of infection with consequent increased efficacy. It has also been demonstrated that subinhibitory concentrations of certain drugs can influence bacterial expression of structural and soluble virulence factors. Alterations of this kind have been shown to potentiate bacterial susceptibility to phagocytosis. Notwithstanding these in-vitro examples of immunomodulation, definite proof of clinical benefit is still lacking.
细胞因子作为可能的治疗药物的出现，激发了人们对新旧抗生素的研究，以探讨它们除了主要的杀菌或抑菌活性之外，作为免疫调节剂的潜在活性。此类研究主要集中在外周血细胞（如多形核白细胞和单核细胞）的体外功能上。已对不同抗生素的分级剂量进行了测试，以考察它们影响趋化性、吞噬摄取和杀伤等功能，以及特定生化机制（如超氧化物生成）的能力。结果表明，这些药物对宿主防御功能无影响（β-内酰胺类），或会抑制免疫功能（四环素类和替考拉宁），或与免疫系统显示协同作用（大环内酯类和喹诺酮类），或增强免疫功能（某些头孢菌素类）。在一些情况下，已证明在治疗范围之外的药物浓度下也具有生物学活性。此外，人们已经认识到，许多药物可以在吞噬细胞内浓缩，并由此被转运至感染部位，从而提高疗效。还已证明，某些药物的亚抑菌浓度可影响细菌结构和可溶性毒力因子的表达。已表明这种改变可增强细菌对吞噬作用的敏感性。尽管有这些体外免疫调节的例子，但仍缺乏临床获益的确切证据。
