ACTIVATED T-CELLS AND CYTOKINES IN BRONCHOALVEOLAR LAVAGES FROM PATIENTS WITH VARIOUS LUNG-DISEASES ASSOCIATED WITH EOSINOPHILIA

Increasing evidence suggests an important role for cytokines in the re gulation of eosinophilic inflammation. In the present study we investi gated the distribution of leukocytes, lymphocyte subsets, their activa tion state, and the cytokine profile present in BAL fluid from patient s with various lung diseases associated with eosinophilia. For this pu rpose, we analyzed the levels of IL-1 beta, IL-2, IL-4, IL-5, IL-6, IL -8, GM-CSF, TNF-alpha, and IFN-gamma, as well as soluble IL-2 and TNF receptors, in concentrated bronchoalveolar lavage (BAL) fluid obtained from clearly defined patients with allergic and nonallergic asthma, e osinophilic pneumonia, allergic bronchopulmonary aspergillosis (ABPA), hypersensitivity pneumonitis, and idiopathic pulmonary fibrosis. BAL fluid from normal individuals and sarcoidosis patients was analyzed as noneosinophilic controls. BAL cytokine levels were compared with the cellular infiltrate and the activation state of CD4(+) and CD8(+) T ce lls as measured by the expression of IL-2 receptors (CD25), HLA-DR, an d the very late activation antigen VLA-1. Beside the characteristic le ukocyte infiltrate in the various lung diseases, all patients demonstr ated significantly increased numbers of activated CD4 and CD8 T cells compared with normal individuals. The analysis of the cytokine profile present in BAL fluid revealed a T helper type 2 (Th2) cell cytokine p attern, with elevated IL-4 and IL-5 but normal levels of IL-2 or IFN-g amma in allergic asthma. ABPA patients demonstrated significantly incr eased levels of IL-4 and IL-5, with low but significantly elevated con centrations of IL-2 and IFN-gamma. In contrast, the analysis of the cy tokine profile in sarcoidosis patients revealed a Th1 cell cytokine pa ttern characterized by increased concentrations of IL-2 and IFN-gamma but normal levels of IL-4 or IL-5. All other patient groups showed a c ytokine pattern incompatible with a pure Th1 or Th2 cell response, bec ause IL-5, IL-2, and IFN-gamma were found to be significantly increase d. The BAL fluid analysis of the other, mainly non-T cell-derived cyto kines and soluble receptors showed increased levels in all patients co mpared with normal individuals and may represent the ongoing inflammat ory responses. In conclusion, whereas increased IL-4 levels were found only in diseases characterized by increased IgE production, IL-5 was elevated in all patients with increased numbers of eosinophils. The do se correlation between IL-5 levels, number of eosinophils, and activat ed T cells further supports a role for IL-5 in causing tissue eosinoph ilia.