INCREASED EXPRESSION OF THE INTERLEUKIN-10 GENE BY ALVEOLAR MACROPHAGES IN INTERSTITIAL LUNG-DISEASE

Idiopathic pulmonary fibrosis (IPF) and bronchiolitis obliterans with organizing pneumonia (BOOP) are interstitial lung diseases of unknown pathogenesis. Alveolar macrophages play a major role in the regulation of the inflammatory response in these diseases through their ability to produce cytokines that modify the inflammatory response. Tumor necr osis factor-alpha (TNF-alpha) and interleukin-10 (IL-10) exhibit proin flammatory and anti-inflammatory actions, respectively, and thus an im balance in the expression of these cytokines may contribute to the pat hogenesis of IPF and BOOP. Therefore, we quantified IL-10 and TNF-alph a mRNA levels in alveolar macrophages obtained by bronchoalveolar lava ge (BAL) from patients with IPF and BOOP and in normal healthy volunte ers. The level of TNF-alpha mRNA in macrophages obtained from IPF and BOOP patients was not significantly different from normal healthy subj ects. However, macrophages from patients with IPF and BOOP expressed i ncreased levels of IL-10 mRNA compared with healthy controls. In addit ion, stimulation of alveolar macrophages with lipopolysaccharide in th e presence of a neutralizing anti-IL-10 antibody augmented the product ion of TNF-alpha over that seen in the absence of anti-IL-10 antibody, suggesting that the increased expression of IL-10 by alveolar macroph ages may act to control the expression of TNF-alpha. Paradoxically, me asurement of IL-10 protein in cell-free BAL fluid revealed lower amoun ts of the protein in patients with IPF and BOOP compared with healthy controls.