Pituitary Adenylate Cyclase-Activating Polypeptide Deficiency Enhances Oxazolone-Induced Allergic Contact Dermatitis in Mice

Abstract

Pituitary adenylate cyclase-activating polypeptide (PACAP) is present in capsaicin-sensitive sensory neurons and inflammatory/immune cells, therefore it is suggested to play a role in neuro-immune interactions. Our aim was to investigate the role of PACAP in oxazolone-induced delayed-type hypersensitivity reaction in the skin using deficient mice (PACAP(-/-)). Sensitization was induced by 2% oxazolone application on the shaved abdomen on two consecutive days; inflammation was elicited by oxazolone smearing on the ears 6days later. Ear thickness was measured by micrometry. Histological examination, cytokine profile [IL-2, IL-4, IL-5, and monocyte chemoattractant protein-1: MCP-1, IFN-γ, tumor necrosis factor alpha (TNF-α)] and myeloperoxidase activity correlating with the number of neutrophils/macrophages were determined 24 and 48h later. Oxazolone induced a 110-130% swelling after 24-48h in wild-type mice, which was significantly greater in PACAP-deficient mice. Histological analysis confirmed markedly increased edema in PACAP(-/-) mice, but the moderately enhanced inflammatory cell accumulation was not statistically significant compared with the wild-types. There was no difference in myeloperoxidase activity of the ear homogenates. Elevation of MCP-1, but not the levels of the other cytokines, was significantly higher in the samples of the PACAP-deficient mice. These results suggest that PACAP exerts anti-inflammatory, particularly edema-inhibiting effects in allergic contact dermatitis.