title: Interleukin 13 and the beta-adrenergic blockade theory of asthma revisited 40 years later.
abstract: BACKGROUND
  Beta2-Adrenergic agonists are the most potent agents clinically used in inhibiting and preventing the immediate response to bronchoconstricting agents and in inhibiting mast cell mediator release. This raises the possibility that an abnormality in beta-adrenergic receptor function or circulating catecholamine levels could contribute to airway hyperresponsiveness.
  
  
  OBJECTIVE
  To link interleukin 13 (IL-13) to the pathogenesis of asthma.
  
  
  METHODS
  Almost 4 decades ago, Andor Szentivanyi published a beta-adrenergic theory of atopic abnormality in bronchial asthma. He proposed 9 characteristics to define bronchial asthma. Because he published these 9 tenets of the beta-adrenergic blockade theory of asthma in 1968, it is appropriate and important to evaluate their relevance in light of advances in pharmacology, inflammation, and immunology.
  
  
  RESULTS
  We describe the effects of the allergic reaction on beta-adrenergic responses and airway responsiveness. Both IL-1beta and tumor necrosis factor a have been detected in increased amounts in bronchial lavage fluids in allergic airway inflammation. Both IL-13 and the proinflammatory cytokines IL-1beta and tumor necrosis factor a have been demonstrated in airway smooth muscle to cause a decreased relaxation response to beta-adrenergic agonist. However, IL-13 has been shown to be necessary and sufficient to produce the characteristics of asthma.
  
  
  CONCLUSIONS
  The decreased adrenergic bronchodilator activity and associated hypersensitivity to mediators put forth by Szentivanyi can be elicited with IL-13 and support its role in the pathogenesis of asthma.
authors.affiliation: Division of Allergy/Immunology, Department of Medicine, Creighton University, Omaha, Nebraska 68131, USA. rtownley@creighton.edu
authors.forename: Robert G
authors.initials: RG
authors.lastname: Townley
mesh_terms: D058672:Adrenergic beta-2 Receptor Antagonists; D000319:Adrenergic beta-Antagonists / Q000494:pharmacology; D000818:Animals; D001249:Asthma / Q000503:physiopathology*; D016207:Cytokines / Q000378:metabolism / Q000494:pharmacology; D006801:Humans; D018793:Interleukin-13 / Q000502:physiology*; D008954:Models, Biological; D018343:Receptors, Adrenergic, beta-2 / Q000502:physiology*; D012130:Respiratory Hypersensitivity / Q000503:physiopathology; D012137:Respiratory System / Q000187:drug effects / Q000378:metabolism / Q000503:physiopathology
chemical_list: D058672:Adrenergic beta-2 Receptor Antagonists; D000319:Adrenergic beta-Antagonists; D016207:Cytokines; D018793:Interleukin-13; D018343:Receptors, Adrenergic, beta-2