Antibiotics and neutrophil function--potential immunomodulating activities

Abstract

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.