Frontline: Inhibition of allergen‐induced pulmonary inflammation by the tripeptide feG: a mimetic of a neuro‐endocrine pathway

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Abstract
Interactions between the neuro‐endocrine system and immune system help maintain health. One interaction involves the superior cervical ganglia (SCG), which regulate the prohormone submandibular rat 1 (SMR1) produced by the submandibular gland (SMG). A peptide derived from SMR1, feG, has anti‐inflammatory activity, and modification to D‐isomer feG enhances bioactivity. We tested feG as a therapeutic agent for airways inflammation, using rats sensitized by OVA or Nippostrongylus brasiliensis (Nb). Treatment with feG but not fdG down‐regulated OVA‐challenge‐induced increases in bronchoalveolar lavage (BAL)‐derived macrophages, eosinophils and PMN (neutrophils) by 44%, 69% and 67%, respectively, at 24 h. We found that feG also reduced ICAM‐1 on BAL‐derived macrophages and eosinophils by 27% and 65%, and L‐selectin on PMN by 55% following OVA challenge. Furthermore, feG but not fdG reduced the OVA‐induced TNF increase in BAL fluid. We showed that feG also down‐regulated both hyper‐responsiveness to methacholine (by 27%) and microgranulomata formation in the lung parenchyma. In Nb‐challenged rats, feG treatment inhibited ex vivo allergen‐induced contraction of tracheal smooth muscle by up to 73%. In conclusion, feG, which is a mimetic of a peptide derived from a rat salivary gland prohormone, has anti‐inflammatory properties in allergic airways inflammation in Brown‐Norway rats. The role of the SCG‐SMG neuro‐endocrine pathway in allergic asthma and other inflammatory diseases requires additional study.