Fine tuning host responses in the face of infection: emerging roles and clinical applications of host defence peptides.

Abstract

Host defence peptides (HDPs) are powerful modulators of human innate immunity, and can modify the outcome of the endogenous host response to infection. The progressive development of pathogen resistance to conventional antimicrobial agents has lead to a new appreciation of HDPs for their ability to fight infection, enhance vaccine responses, limit infl ammation and promote wound healing, within the context of human disease. HDPs are a family of cationic, short, amphipathic peptides that include the classical mammalian antimicrobial peptides, cathelicidins and defensins, as well as non-antimicrobial peptides with similar immunomodulatory properties. This chapter reviews our current basic understanding of the anti-infective and immunomodulatory properties of both endogenous HDPs and synthetic derivatives (termed innate defence regulators) with regard to their ability to selectively fine tune the responses of host cells and physiology. The clinical application of these molecules is also discussed, with a focus on past and ongoing clinical trials of HDPs and innate defence regulators as novel therapeutics for infectious and infl ammatory diseases.