title: Food restriction-mediated adrenal influences on antigen-induced bronchoconstriction and airway eosinophil influx in the guinea pig.
abstract: The aim of this study was to measure the effects of food restriction on antigen-induced bronchoconstriction and inflammatory cell influx in guinea pigs and to determine the role of plasma cortisol and catecholamine concentrations. Ovalbumin (OA; 0.3 mg/kg, i.v.) was administered to OA-sensitized, anesthetized guinea pigs which had been allowed free access to food or had been food restricted for 18 h prior to OA challenge. In addition to higher plasma levels of epinephrine (30% increase) and cortisol (33% increase), fasted guinea pigs had significantly lower (60% decreased) maximal bronchoconstrictor responses to OA than nonfasted, sensitized litter mates. Additionally, groups of fasted or fed animals were subdivided into two additional treatment groups: (1) saline-pretreated or (2) polyethylene glycol 400 (PEG)-pretreated (1 ml/kg, p.o., 1 h prior to antigen challenge). In saline-treated, fasted animals, bronchoconstrictor responses to antigen were significantly diminished (67% decreased) and epinephrine and cortisol levels were increased (64 and 34%, respectively) compared to the corresponding fed group. In both fasted and fed groups, the PEG-treated guinea pigs had higher plasma epinephrine and cortisol levels than animals which received saline, but no significant differences were detected within the PEG-treated group. Plasma norepinephrine concentrations were lower in all fasted groups. In a separate model in conscious guinea pigs, there were no differences in aerosol OA-induced bronchoconstriction and eosinophil influx between fasted and fed groups. However, compared to the saline pretreatment group, PEG administration reduced the antigen-induced bronchoconstriction and eosinophilia in both fed and fasted guinea pigs. We speculate that the reduced responsiveness to antigen in fasted versus fed animals may result from food-restriction-induced, stress-related release of epinephrine and cortisol from the adrenal glands, thereby suppressing mast cell degranulation or reducing responsiveness to spasmogenic and chemotactic mediators. In addition, the results suggest that oral dosing with 100% PEG may enhance this phenomenon.
authors.affiliation: Department of Pulmonary Pharmacology, SmithKline Beecham Pharmaceuticals, King of Prussia, Pa., USA.
authors.forename: D C
authors.initials: DC
authors.lastname: Underwood
authors.forename: J K
authors.initials: JK
authors.lastname: Matthews
authors.forename: R R
authors.initials: RR
authors.lastname: Osborn
authors.forename: D W
authors.initials: DW
authors.lastname: Hay
mesh_terms: D000280:Administration, Inhalation; D000311:Adrenal Glands / Q000276:immunology* / Q000502:physiology; D000336:Aerosols; D000758:Anesthesia; D000818:Animals; D000941:Antigens / Q000008:administration & dosage / Q000276:immunology / Q000494:pharmacology*; D001980:Bronchi / Q000166:cytology / Q000276:immunology; D016084:Bronchoconstriction / Q000276:immunology*; D002395:Catecholamines / Q000097:blood; D002465:Cell Movement / Q000276:immunology*; D004804:Eosinophils / Q000166:cytology / Q000276:immunology*; D004837:Epinephrine / Q000097:blood; D005508:Food Deprivation / Q000502:physiology*; D006168:Guinea Pigs; D006854:Hydrocortisone / Q000097:blood; D007275:Injections, Intravenous; D008297:Male; D010047:Ovalbumin / Q000008:administration & dosage / Q000276:immunology; D011092:Polyethylene Glycols / Q000008:administration & dosage
chemical_list: D000336:Aerosols; D000941:Antigens; D002395:Catecholamines; D011092:Polyethylene Glycols; D010047:Ovalbumin; D006854:Hydrocortisone; D004837:Epinephrine