title: Effect of IL-1β and TNF-α vs IL-13 on bronchial hyperresponsiveness, β2-adrenergic responses and cellularity of bronchial alveolar lavage fluid.
abstract: 1 Levels of IL-13, IL-1β and TNF-α are increased in bronchial lavage fluid of asthmatics and induce certain significant features of bronchial asthma including airway hyper-responsiveness (AHR). In this study, we have investigated the effect of these cytokines in naïve mice and those sensitized to ovalbumin (OVA) on bronchoconstrictions to methacholine (MCh) and the functional antagonism induced by β2 -adrenoceptor agonism. 2 Naïve or OVA-sensitized mice were treated for 3 days with IL-1β (250 U), TNF-α (150 ng), IL-13 (5 μg) or combinations of IL-1β with TNF-α or IL-1β with IL-13. MCh-induced bronchoconstriction and its sensitivity to albuterol, a β2-adrenoceptor agonist, was assessed 24 h after the last cytokine administration. 3 In naïve mice, responsiveness to MCh was significantly increased by the combination of IL-1β and TNF-α, IL-13 alone or in combination with IL-1β, but not by treatment with IL-1β or TNF-α alone. Similar results were obtained in OVA-sensitized mice except that treatment with IL-13 alone did not increase sensitivity to MCh. 4 In naïve mice, albuterol sensitivity was only significantly attenuated by treatment with IL-1β and TNF-α in combination. In mice sensitized to OVA, albuterol sensitivity was significantly attenuated by treatment with TNF-α, IL-13 or IL-13 in combination with IL-1β. 5 Inflammatory cell influx was increased by all cytokines and combinations except IL-13 in OVA-sensitized mice. 6 Our data do not support a link between inflammatory cell influx and AHR. In addition, the mechanism of IL-13-induced AHR might involve decreased β2-adrenoceptor responsiveness.
authors.affiliation: Division of Asthma, Allergy and Immunology, Creighton University School of Medicine, Omaha, NE, USA.
authors.forename: M
authors.initials: M
authors.lastname: Horiba
authors.forename: N
authors.initials: N
authors.lastname: Qutna
authors.forename: P
authors.initials: P
authors.lastname: Gendapodi
authors.forename: S
authors.initials: S
authors.lastname: Agrawal
authors.forename: K
authors.initials: K
authors.lastname: Sapkota
authors.forename: P
authors.initials: P
authors.lastname: Abel
authors.forename: R G
authors.initials: RG
authors.lastname: Townley
mesh_terms: D058666:Adrenergic beta-2 Receptor Agonists / Q000494:pharmacology* / Q000627:therapeutic use; D000420:Albuterol / Q000037:antagonists & inhibitors / Q000494:pharmacology / Q000627:therapeutic use; D000818:Animals; D016535:Bronchial Hyperreactivity / Q000188:drug therapy*; D001992:Bronchoalveolar Lavage Fluid / Q000166:cytology*; D016084:Bronchoconstriction / Q000187:drug effects* / Q000502:physiology; D016085:Bronchoconstrictor Agents / Q000037:antagonists & inhibitors / Q000494:pharmacology; D001993:Bronchodilator Agents / Q000037:antagonists & inhibitors / Q000494:pharmacology; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D004347:Drug Interactions; D006801:Humans; D018793:Interleukin-13 / Q000494:pharmacology*; D053583:Interleukin-1beta / Q000494:pharmacology*; D008297:Male; D016210:Methacholine Chloride / Q000037:antagonists & inhibitors / Q000494:pharmacology; D051379:Mice; D008807:Mice, Inbred BALB C; D010047:Ovalbumin / Q000009:adverse effects; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology*
chemical_list: D058666:Adrenergic beta-2 Receptor Agonists; D016085:Bronchoconstrictor Agents; D001993:Bronchodilator Agents; D018793:Interleukin-13; D053583:Interleukin-1beta; D014409:Tumor Necrosis Factor-alpha; D016210:Methacholine Chloride; D010047:Ovalbumin; D000420:Albuterol