Systemic murine cathelicidin CRAMP safely attenuated colonic neutrophil infiltration in pigs

Abstract

Post-weaning diarrheic colitis, often caused by enteropathogens, are severe and potentially lethal diseases in young pigs. Conventional treatment with antibiotics is problematic due to increasing prevalence of multi-drug resistant bacteria. Few alternative treatments exist, so development of antibiotic-free therapies is urgently needed for livestock. Cathelicidin peptides, produced by epithelial cells and neutrophils, are microbicidal compounds capable of modulating innate immune and inflammatory responses. However, the effects of exogenous cathelicidin on gut homeostasis is poorly understood in pigs. We administered the murine cathelicidin CRAMP systemically to healthy pigs, to establish the peptide's safety and assess its ability to modulate colonic mucosal defenses. A single intraperitoneal injection of CRAMP was well tolerated up to two weeks and pigs remained clinically healthy. CRAMP caused some alteration of mucus glycosylation patterns in the colon by increasing sialylated mucins (P < 0.05) and decreased neutrophil influx close to the epithelium (P < 0.001). This study supports further investigation of CRAMP as an immunomodulatory treatment for infectious colitis in pigs.

Keywords: CRAMP; Cathelicidin; Colonic mucus; Neutrophil; Post-weaning diarrhea; Swine.