Balance between proinflammatory cytokines and their inhibitors in bronchial lavage from patients with status asthmaticus

Am J Respir Crit Care Med. 1999 Feb;159(2):487-94. doi: 10.1164/ajrccm.159.2.9805115.


Status asthmaticus (SA) is an acute respiratory failure combining an acute bronchospastic reaction with a severe airway inflammation. We previously reported an important influx of neutrophils and an increased secretion of interleukin-8 (IL-8) in patients with SA. The aim of this prospective study was to evaluate in bronchial lavage (BL) of patients with SA (n = 9) under mechanical ventilation (MV) the concentrations of cytokines and related mediators which have the ability to modulate inflammation, either proinflammatory (interleukin-1beta [IL-1beta], IL-6, tumor necrosis factor-alpha [TNF-alpha]), or anti-inflammatory mediators (IL-10, transforming growth factor-beta1 [TGF-beta1]), interleukin-1 receptor antagonist [IL-1Ra], soluble TNF receptor I and II [sTNFRI and II]). To determine the relative importance of both pro- and anti-inflammatory mediators, the net inflammatory activity was analyzed by the capacity of BL fluids (BLF) to increase intercellular adhesion molecule-1 (ICAM-1) expression in the human lung A549 epithelial cell line. These data were compared with those obtained from patients who required MV without respiratory disease (V, n = 4), controlled asthma (A, n = 11), and nonsmoking healthy volunteers (C, n = 8). Levels of IL-1, IL-6, TNF-alpha, and of the active form of TGF-beta1 were significantly higher in SA compared with the other groups. The concentrations of IL-1Ra, IL-10, the latent form of TGF-beta1, and of the sTNFRI and II were not significantly different between SA and V, albeit higher in SA than in A and C. The ratio between IL-1Ra and IL-1beta was significantly higher in patients with SA compared with the other groups, whereas there was no difference for the ratio between both types of sTNFR and TNF-alpha. Despite a marked increase of anti-inflammatory mediators in BL from patients with SA, the net inflammatory activity was found to be proinflammatory and mainly due to the presence of bioactive IL-1beta (79% inhibition of ICAM-1 expression with anti-IL-1beta antibodies) and to a lesser extent TNF-alpha (32% inhibition with anti-TNF-alpha antibodies).

Publication types

  • Comparative Study

MeSH terms

  • Adult
  • Antigens, CD / metabolism
  • Biomarkers
  • Bronchoalveolar Lavage
  • Bronchoalveolar Lavage Fluid / chemistry*
  • Bronchoalveolar Lavage Fluid / cytology
  • Bronchoscopy
  • Cytokines / metabolism*
  • Enzyme-Linked Immunosorbent Assay
  • Female
  • Humans
  • Interleukin 1 Receptor Antagonist Protein
  • Interleukin-1 / metabolism
  • Interleukin-10 / metabolism
  • Interleukin-6 / metabolism
  • Male
  • Middle Aged
  • Receptors, Tumor Necrosis Factor / metabolism
  • Receptors, Tumor Necrosis Factor, Type I
  • Respiration, Artificial
  • Sialoglycoproteins / metabolism
  • Status Asthmaticus / metabolism*
  • Status Asthmaticus / pathology
  • Status Asthmaticus / therapy
  • Transforming Growth Factor beta / metabolism
  • Tumor Necrosis Factor-alpha / metabolism


  • Antigens, CD
  • Biomarkers
  • Cytokines
  • IL1RN protein, human
  • Interleukin 1 Receptor Antagonist Protein
  • Interleukin-1
  • Interleukin-6
  • Receptors, Tumor Necrosis Factor
  • Receptors, Tumor Necrosis Factor, Type I
  • Sialoglycoproteins
  • Transforming Growth Factor beta
  • Tumor Necrosis Factor-alpha
  • Interleukin-10