SUPPRESSIVE MECHANISMS OF ALVEOLAR MACROPHAGES IN INTERSTITIAL LUNG-DISEASES - ROLE OF SOLUBLE FACTORS AND CELL-TO-CELL CONTACT

Alveolar macrophages (AMs) from patients with interstitial lung diseas es, such as sarcoidosis and idiopathic pulmonary fibrosis, suppress th e phytohaemagglutinin (PHA) stimulation of autologous peripheral lymph ocytes. The aim of this study was to determine whether the suppressive effect of alveolar macrophages of patients with interstitial lung dis ease is due, not only to the secretion of soluble factors prostaglandi n E2 (PGE2), interleukin-1 (IL-1) but is also correlated to a direct e ffect of AMs on the expression of IL-2 receptors (IL-2R: CD25) and on the induction of IL-2 activity. We studied 26 subjects, 8 with sarcoid osis, 7 with idiopathic pulmonary fibrosis, and 11 controls. Alveolar macrophages of sarcoid and idiopathic pulmonary fibrosis patients supp ressed proliferation of autologous peripheral lymphocytes by 68+/-14% and 53+/-4.5%, respectively, compared to enhancement of 19+/-11% in th ree controls and suppression of 25+/-11% in the other six controls; th e difference between subjects with interstitial lung disease and contr ols was significant. As already reported, the alveolar macrophages of sarcoid patients secreted large amounts of IL-1 (184+/-59 U.ml-1) wher eas the alveolar macrophages from idiopathic pulmonary fibrosis patien ts secreted large amounts of PGE2 (3.6+/-2 ng.ml-1.10(-5) cells) compa red with 23+/-19 U.ml-1 IL-1 and 0.34+/-0.15 ng.ml-1-10(-5) cells resp ectively, of controls. Suppression by supernatants recovered from lipo polysaccharide (LPS) stimulated alveolar macrophages can only partiall y explain the high suppressive effect of alveolar macrophages of inter stitial lung diseases. Co-culture of autologous peripheral lymphocytes with alveolar macrophages of sarcoid and idiopathic pulmonary fibrosi s patients markedly reduced the expression of CD25 (down to 66% of the initial value) and decreased induction of IL-2 activity (down to 47% of the initial value). We conclude that alveolar macrophages of patien ts with sarcoidosis and idiopathic pulmonary fibrosis suppress express ion of IL-2R and decrease induction of IL-2 activity mainly by cell-to -cell contact.