Tumour necrosis factor-alpha potentiates contraction of human bronchus in vitro

Respirology. 2001 Sep;6(3):199-203. doi: 10.1046/j.1440-1843.2001.00334.x.

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.

Methodology: 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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Acetylcholine / pharmacology
  • Bronchi / physiology
  • Humans
  • Muscle Contraction / physiology*
  • Muscle, Smooth / physiology*
  • Tumor Necrosis Factor-alpha / physiology*

Substances

  • Tumor Necrosis Factor-alpha
  • Acetylcholine