PRODUCTION OF GRANULOCYTE-MACROPHAGE COLONY-STIMULATING FACTOR IN HUMAN AIRWAYS DURING ALLERGEN-INDUCED LATE-PHASE REACTIONS IN ATOPIC SUBJECTS

Granulocyte-macrophage colony-stimulating factor (GM-CSF) and interleu kin-3 (IL-3) are hematopoietic growth factors that have been shown to induce proliferation and activation of inflammatory cells, and may pla y a role in allergic reactions. Since little is known about the involv ement of cytokines in allergic inflammation in the lung, the levels of GM-CSF and IL-3 were measured in bronchoalveolar lavage (BAL) fluids obtained in the late phase after segmental lung antigen (Ag) challenge in 14 allergic rhinitis subjects with or without bronchial asthma. BA L fluids either after Ag (ragweed, dust mite, or timothy) or saline co ntrol challenge were recovered 19 h later. In 6 of the 14 patients, BA L fluids were concentration-dialyzed (20x) and assayed for cytokine ac tivity. Cytokine assays were performed using the human megakaryocytic leukemic cell line M-07e, which is responsive to either GM-CSF or IL-3 . The level of GM-CSF-equivalents was approximately 25 times higher in Ag-challenged sites (49.9 +/- 12.7 pg/ml; mean +/- SEM), compared to saline challenge sites (2.2 +/- 1.0, p < 0.01, n = 9). Neutralization experiments using a polyclonal specific antibody (Ab) against GM-CSF a nd IL-3 revealed that the bulk of the activity was GM-CSF. BAL fluids from Ag- and saline-challenged sites in one nonatopic subject containe d no significant GM-CSF activity. Furthermore, the level of GM-CSF in Ag-challenged BAL fluid and the percentage of eosinophils in BAL from each subject correlated significantly (r = 0.73, p < 0.005, n = 14). W e conclude that GM-CSF is produced in the human airway during the late phase after Ag challenge in allergic subjects. These results suggest that this cytokine may play a role in the development of the late phas e reaction following experimental Ag challenge.