Neurotensin-based hybrid peptide's anti-inflammatory activity in murine model of a contact sensitivity response

The objective of the study was to investigate the possibility of modulation of skin inflammation by topical treatment with a novel compound: an opioid-neurotensin hybrid peptide PK20 encompassing endomorphin-2 analog and modified fragment of neurotensin (8-13). Contact sensitivity response was induced in mice by skin sensitization with dinitrofluorobenzene (DNFB) followed by topical hapten application on ears. Mice were treated locally with PK20 or pure cream 2h after the challenge with DNFB. 2 and 24h after hapten exposure, ear thickness was determined. Ears were collected for histology and homogenization. Supernatants were used for measurement of contents of cytokines and lipid peroxidation products. Treatment with PK20 reduced significantly the late phase of contact sensitivity response, which was revealed by ear thickness diminution and reduction of inflammatory cell infiltration. The average concentrations of IL-1α, MCP-1, TNF-α and thiobarbituric acid-reactive substances were significantly decreased in the ears treated with the chimera in comparison to the control cream treated ears in DNFB sensitized/DNFB challenged group. We found that PK20 topical treatment alleviates hypersensitivity responses triggered by DNFB challenge and usage of the hybrid peptide may be a novel therapeutic strategy in the treatment of chronic inflammatory diseases. However, the mechanism remains unclear and needs further investigation.