title: Tumour necrosis factor-alpha potentiates contraction of human bronchus in vitro.
abstract: OBJECTIVE
  Chronic inflammation of the airways is an important component in the induction of airway hyperresponsiveness (AHR) in asthma. The pro-inflammatory cytokines interleukin-1beta (IL-1beta) and tumour necrosis factor-alpha (TNF-alpha) have been implicated in the induction of AHR. Whether these cytokines directly modulate the contractile properties of human airway smooth muscle (ASM) has not been fully investigated.
  
  
  METHODS
  The contractile response to acetylcholine (ACh) (10(-8) to 10(-3) mol/L) was determined in isolated human bronchial segments both prior to and following a 16-h incubation period with IL-1beta (10 or 20 ng/mL) and TNF-alpha (25 ng/mL), either alone or in combination. Incubation of human bronchial segments with IL-1beta/TNF-alpha was also performed in the presence of the COX-1/COX-2 inhibitor, indomethacin.
  
  
  RESULTS
  Tumour necrosis factor-alpha potentiated the contractile response to ACh by approximately 27%, while IL-1beta or the cytokines in combination had no effect. Indomethacin had no modulatory effect on the contractile response to ACh in the cytokine-treated tissues.
  
  
  CONCLUSIONS
  The relative concentrations of IL-1beta/TNF-alpha in the vicinity of ASM may ultimately determine their effects on ASM contraction in asthma.
authors.affiliation: Respiratory Research Group, Faculty of Pharmacy and Department of Pharmacology, University of Sydney, New South Wales, Australia.
authors.forename: M B
authors.initials: MB
authors.lastname: Sukkar
authors.forename: J M
authors.initials: JM
authors.lastname: Hughes
authors.forename: C L
authors.initials: CL
authors.lastname: Armour
authors.forename: P R
authors.initials: PR
authors.lastname: Johnson
mesh_terms: D000109:Acetylcholine / Q000494:pharmacology; D001980:Bronchi / Q000502:physiology; D006801:Humans; D009119:Muscle Contraction / Q000502:physiology*; D009130:Muscle, Smooth / Q000502:physiology*; D014409:Tumor Necrosis Factor-alpha / Q000502:physiology*
chemical_list: D014409:Tumor Necrosis Factor-alpha; D000109:Acetylcholine