CC chemokines and interleukin-5 in bronchial lavage fluid from patients with status asthmaticus. Potential implication in eosinophil recruitment.

Abstract

In status asthmaticus (SA), severe bronchial inflammation is associated with acute respiratory failure. Neutrophils are the prominent cells found in bronchi from SA patients, but eosinophils are also recruited within the first 48 h after the beginning of mechanical ventilation (MV). Interleukin (IL)-5 and CC chemokines have been directly implicated in the pathophysiology of allergic asthma. However, their involvement in SA had not been determined. The aim of this study was to evaluate the production of CC chemokines and of IL-5 in airways from ventilated patients with SA as compared with mild asthma (A), and to assess the role of these mediators in eosinophil recruitment. We measured levels of the chemokines monocyte chemotactic proteins (MCPs)-1 and -3; regulated on activation, normal T-cell expressed and secreted (RANTES); macrophage inflammatory peptide (MIP)-1alpha; and eotaxin; and of the cytokine IL-5 in bronchial lavage fluid (BLF) from 10 SA patients, four patients without respiratory disease but undergoing ventilation (V) who were receiving MV, 11 patients with A, and eight healthy volunteers (C). We further evaluated in vitro eosinophil chemotactic activity of BLF from the various groups. Levels of MCP-1, MIP-1alpha, RANTES, and IL-5 were significantly higher in the SA than in the V, A, and C groups. MCP-3 and eotaxin values were not significantly different in the SA and other groups; however, their levels, as well as those of MIP-1alpha, RANTES, and IL-5 correlated with eosinophil influx. Eosinophil chemotactic activity in BLF was increased in asthmatic subjects (A and SA groups) as compared with the other groups, and in SA patients as compared with A patients. Addition of neutralizing anti-IL-5, anti-MCP-3, anti-eotaxin, and anti-RANTES antibodies significantly inhibited the eosinophil chemotactic activity as compared with that of native BLF. This study shows that the levels of various CC chemokines and IL-5 are increased in airways of SA patients, and are potentially involved in eosinophil recruitment.