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Am. J. Respir. Crit. Care Med., Volume 159, Number 2, February 1999, 487-494

Balance between Proinflammatory Cytokines and Their Inhibitors in Bronchial Lavage from Patients with Status Asthmaticus

ISABELLE TILLIE-LEBLOND, JÉRÔME PUGIN, CHARLES-HUGO MARQUETTE, CATHERINE LAMBLIN, FABIENNE SAULNIER, ANNE BRICHET, BENOIT WALLAERT, ANDRÉ-BERNARD TONNEL, and PHILIPPE GOSSET

Unité INSERM U 416, Institut Pasteur de Lille, Lille; Clinique des Maladies Respiratoires, CHRU, Lille; Service de Réanimation, Hôpital Calmette, CHRU, Lille, France; and Division des Soins Intensifs de Médecine, University Hospital, Geneva, Switzerland

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-beta 1 [TGF-beta 1]), 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-beta 1 were significantly higher in SA compared with the other groups. The concentrations of IL-1Ra, IL-10, the latent form of TGF-beta 1, 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).




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