Aims: 

Substance P (SP) and neurokinin A (NKA) encoded by the preprotachykinin A (TAC1) gene in sensory neurones, epithelial and inflammatory cells are involved in neurogenic inflammation via predominantly neurokinin 1 and 2 (NK1 and NK2) receptor activation, respectively. Hemokinin-1 (HK-1) derived from the TAC4 gene in immune cells also have remarkable selectivity and potency for the NK1 receptor. Neuro-immune interactions play an important role in inflammatory bowel diseases. We investigated the role of the tachykinin system in the dextran-sulphate sodium (DSS)-induced colitis model with TAC1, TAC4, and TAC1/TAC4 gene deficient (KO) mice.

Methods: 

DSS (2%) was administered orally for 7 days, control animals received tap water. Body weight changes, stool consistency and fecal blood content were evaluated every day and the Disease Activity Index (DAI) was calculated. Semiquantitative histological evaluation, myeloperoxidase (MPO) activity measurement and IL-1beta determination were performed from the distal colon samples removed on day 7.

Results: 

DSS drinking induced bloody diarrhea and weight loss, MPO and IL-1beta elevation, as well as remarkable inflammatory histopathological changes in C57Bl/6 wild type mice. Significantly lower DAIs were detected from day 6 and smaller histopathological scores were observed in all KO groups. MPO increase correlating with neutrophil/macrophage accumulation was significantly smaller in TAC4 and TAC1/4 KO mice, but IL-1beta production was not influenced in any groups.

Conclusion: 

It can be concluded, that SP, NKA and HK-1 have pro-inflammatory functions in the colon, particularly through neurogenic mechanisms, but HK-1 also promotes neutrophil infiltration.

Support: 

OTKA K81984, K73044, ETT 03-380/2009, SROP-4.2.1.B-10/2/KONV-2010-0002, OTKA