Fusafungine, an antimicrobial with anti-inflammatory properties in respiratory tract infections - Review, and recent advances in cellular and molecular activity

Following bacterial or viral infection, an inflammatory reaction develops that is aimed at the capture and destruction of the pathogens. Although this has a beneficial effect when it develops normally, it can be deleterious and cause tissue damage when it is excessively intense, or when the phenomenon is self-perpetuating. Fusafungine, a combination of several enniatins, displays bacteriostatic activity against most micro-organisms responsible for both infections and superinfections of the respiratory tract. It has been developed for topical oral and/or nasal inhalation treatment. Since early topical treatment of respiratory tract diseases with fusafungine was shown to significantly improve symptoms related to both local and systemic inflammatory reactions, both in clinical trials and in experimental animal models, its mechanism of anti-inflammatory action was investigated in depth at both the molecular and the cellular levels. Fusafungine at low concentrations down-regulates the expression of intercellular adhesion molecule-1 (ICAM-1) but not the chemokine RANTES (regulated upon activation, normal T cell expressed and secreted) by activated macrophages, inhibits the production of the proinflammatory cytokines tumour necrosis factor-alpha, interleukin-1 and interleukin-6, mainly by acting at a post-transcriptional level, and inhibits the release of oxygen free radicals by inflammatory macrophages without altering their phagocytic activity. Fusafungine also inhibits T-cell activation and proliferation, and the synthesis of interferon-gamma by activated T cells. As an antimicrobial drug with anti-inflammatory properties, fusafungine should break the vicious circle of infection and inflammation. Therefore, it is particularly well adapted to management of respiratory tract infections.