Augmentation of functional prostaglandin E levels on the respiratory epithelial surface by aerosol administration of prostaglandin E

Z Borok, A Gillissen, R Buhl, RF Hoyt… - Am Rev Respir …, 1991 - atsjournals.org
Z Borok, A Gillissen, R Buhl, RF Hoyt, RC Hubbard, T Ozaki, SI Rennard, RG Crystal
Am Rev Respir Dis, 1991atsjournals.org
Prostaglandin E (PGE), a cyclooxygenase metabolite normally present in high
concentrations in respiratory epithelial lining fluid (ELF), is capable of suppressing
mesenchymal cell proliferation mediated by polypeptide-derived growth factors. Although
PGEis normally abundant In respiratory ELF, PGE levels In ELF of individuals with idiopathic
pulmonary fibrosis (IPF), a fibrotic lung disorder characterized by intraalveolar mesenchymal
cell accumulation and fibrosis, were found to be 50% lower than normal (p< 0.01): that Is, a …
Summary
Prostaglandin E (PGE), a cyclooxygenase metabolite normally present in high concentrations in respiratory epithelial lining fluid (ELF), is capable of suppressing mesenchymal cell proliferation mediated by polypeptide-derived growth factors. Although PGEis normally abundant In respiratory ELF, PGE levels In ELF of individuals with idiopathic pulmonary fibrosis (IPF), a fibrotic lung disorder characterized by intraalveolar mesenchymal cell accumulation and fibrosis, were found to be 50% lower than normal (p< 0.01): that Is, a relative PGE" deficiency" in ELF may enhance intraalveolar mesenchymal cell proliferation in IPF. With this background, it is rational to consider augmenting PGE levels In ELF as a future therapy for IPF. Since systemic administration of PGE is associated with significant adverse effects, in vitro and experimental animal studies were carried out to evaluate whether aerosol PGEadministration could augment ELF PGElevels. Greater than
50% of a solution of PGE, could be placed in droplets< 3 um mass median aerodynamic diameter without loss of function. Aerosolization of PGE, to sheep (n= 14) resulted in a marked augmentation of ELF PGE, levels (preaerosol 20 ą 7 nM, 30 min postaerosol 1,150 ą 210 nM; p< 0.0 to
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