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

In status asthmaticus (SA), severe bronchial inflammation is associated wit h acute respiratory failure. Neutrophils are the prominent cells found in b ronchi from SA patients, but eosinophils are also recruited within the firs t 48 h after the beginning of mechanical ventilation (MV), Interleukin (IL) -5 and CC chemokines have been directly implicated in the pathophysiology o f allergic asthma. However, their involvement in SE 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 recruit ment. We measured levels of the chemokines monocyte chemotactic proteins (M CPs)-1 and -3; regulated on activation, normal T-cell expressed and secrete d (RANTES); macrophage inflammatory peptide (MIP)-1 alpha; 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) wh o were receiving MV, 11 patients with A, and eight healthy volunteers (C). We further evaluated in vitro eosinophil chemotactic activity of BLF from t he various groups. Levels of MCP-1, MIP-1 alpha, RANTES, and IL-5 were sign ificantly higher in the SA than in the V, A, and C groups. MCP-3 and eotaxi n values were not significantly different in the SA and other groups; howev er, their levels, as well as those of MIP-1 alpha, RANTES, and IL-5 correla ted with eosinophil influx. Eosinophil chemotactic activity in ELF was incr eased in asthmatic subjects (A and SA groups) as compared with the other gr oups, and in SA patients as compared with A patients. Addition of neutraliz ing anti-IL-5, anti-MCP-3, anti-eotaxin, and anti-RANTES antibodies signifi cantly inhibited the eosinophil chemotactic activity as compared with that of native BLF. This study shows that the levels of various CC chemokines an d IL-5 are increased in airways of SA patients, and are potentially involve d in eosinophil recruitment.