Induction of the human cathelicidin LL-37 as a novel treatment against bacterial infections

Review on endogenous antimicrobial peptide induction by (phenyl)butyrate and vitamin D3 as a new anti‐infective strategy. As traditional antibiotics gradually become inefficient, there is a high demand for development of anti‐infectives with a mechanism of action that is different from existing antibiotics. Current antibiotics target the pathogen directly, thereby contributing to the selection of multidrug‐resistant bacterial strains. AMPs, such as the human cathelicidin LL‐37, are small cationic peptides that are part of host defense. They eliminate microbes through diverse mechanisms, thereby contributing to resolution of infections and maintenance of epithelial barrier function. The multiplicity of these mechanisms of action might be a key to restrict the development of resistant bacterial strains. The discovery of LL‐37‐inducing components, such as butyrate and vitamin D3, has opened new avenues to prevent or treat infections. Butyrate and vitamin D3 are potent inducers of LL‐37 but in addition, have many other effects on host immunity. Here, we summarize current data on the effects that LL‐37 and its inducers display on the innate immune response and discuss the feasibility for development of these inducers as possible drugs to prevent or treat infections.