LATE RESPONSE TO ALLERGEN IS ASSOCIATED WITH INCREASED CONCENTRATIONSOF TUMOR-NECROSIS-FACTOR-ALPHA AND IL-5 IN INDUCED SPUTUM

Bronchial antigen challenge of sensitized atopic patients with asthma results in an early fall in FEV1, followed in a proportion of patients by a late (4 to 24 hours) fall, The Late response is accompanied by a n increase in bronchial reactivity, which is widely believed to reflec t local influx and degranulation of inflammatory cells, particularly e osinophils, in association with elevated local secretion of cytokines, We hypothesized that the development of a late-phase bronchoconstrict or response and airway eosinophilia after allergen challenge of sensit ized atopic patients with asthma is associated with elevated induced s putum concentrations of the eosinophil-active cytokines IL-5 and granu locyte-macrophage colony-stimulating factor and the proinflammatory cy tokine tumor necrosis factor-alpha, We counted inflammatory leukocytes and measured cytokine concentrations in induced sputum at baseline an d 24 hours after inhalational allergen challenge of 15 atopic patients with asthma who had previously demonstrated a late response, We obser ved significant increases in the numbers of eosinophils and the concen trations of their granule products, eosinophil cationic protein and eo sinophil peroxidase, In contrast, the numbers of neutrophils and conce ntrations of two of their products, myeloperoxidase and human neutroph il lipocalin, did not significantly change, The numbers of sputum eosi nophils correlated with the maximal late-phase fall in FEV1, Concentra tions of IL-5 and tumor necrosis factor-alpha, but not granulocyte-mac rophage colony-stimulating factor, were significantly elevated after a llergen challenge, We conclude that the relatively noninvasive techniq ue of induced sputum production can be used to monitor the effect of b ronchial provocation on cytokine concentrations in asthma.