Effect of delivery route on pulmonary response to oncostatin M.
The effect of delivery route on lung tissue response to oncostatin M (OM) was evaluated in isolated perfused rat lung (IPRL) and normal human bronchial epithelial cell line BEAS-2B in vitro models. In this study, the extent of induction of the cytokine IL-6 by OM was examined as evidence for local pharmacological activity in response to OM in lung tissue. OM stimulated dose-dependent release of IL-6 in both BEAS-2B cells and IPRL after exposure of either the apical (AP) or basolateral (BL) side of the epithelium. The increase in IL-6 was rapid, beginning 2 h after dosing, and sustained over 48 h. Similar amounts of IL-6 were released to both AP and BL sides of BEAS-2B cells, regardless of the side of OM dosing. However, in IPRL the extent of response of IL-6 induction to OM was always higher at the dosing side. In addition, airway dosing of OM resulted in an overall lower IL-6 response than perfusate dosing, which may result from the low rate of OM transport (<1%/h) across pulmonary epithelium. We conclude that the route of delivery significantly affects the overall extent of the pharmacological response to OM, with a lesser and more localized response after airway delivery to the lung.
Li
Hong Lan
HL
Department of Exploratory Biopharmaceutics and Drug Delivers Pharmaceutical Research Institute, Bristol-Myers Squibb Company, New Brunswick, NJ 08903-0191, USA.
Mathias
Neil
N
Timoszyk
Julita
J
Stouffer
Bruce
B
Wall
Doris
D
D000818:Animals; D000970:Antineoplastic Agents / Q000008:administration & dosage* / Q000493:pharmacokinetics / Q000494:pharmacology*; D002460:Cell Line; D004305:Dose-Response Relationship, Drug; D004797:Enzyme-Linked Immunosorbent Assay; D006801:Humans; D066298:In Vitro Techniques; D015850:Interleukin-6 / Q000378:metabolism; D008168:Lung / Q000187:drug effects* / Q000378:metabolism; D008954:Models, Biological; D053683:Oncostatin M; D010455:Peptides / Q000008:administration & dosage* / Q000493:pharmacokinetics / Q000494:pharmacology*; D051381:Rats
D000970:Antineoplastic Agents; D015850:Interleukin-6; C508351:OSM protein, human; D010455:Peptides; D053683:Oncostatin M