In recent years, the therapeutic potential of antimicrobial peptides (AMPs) as immunomodulators has
become generally accepted. Nevertheless, only very few AMP-based compounds have progressed into clinical
trials. This paradox may be explained by the fact, that some of the intrinsic properties of natural peptides, such as
proteolytic and oxidative instability, render them inconvenient as therapeutics. Therefore, substantial research
efforts have been dedicated to mimic the physico-chemical properties as well as biological activities of AMPs by
designing and identifying more stable peptidomimetics displaying analogous immunomodulatory activity profiles.
Neutrophils play key roles in host defense as major effector cells in clearance of pathogens by phagocytosis
and by regulating other processes of innate immunity as well as by promoting resolution of inflammation. Several
aspects of these effects are correlated to their expression of formyl peptide receptors (FPRs) that have been shown
to be targets of both natural and synthetic antimicrobial peptides. In the present review recent findings highlighting
the role of FPRs in mediating immunomodulatory activities of natural and synthetic AMPs as well as of stabilized
peptidomimetics are discussed, and prospects for future development of immunomodulatory therapeutics are
presented.