Immunology of Fibrotic Lung Disease: Managing Infections Whilst Preventing Autoimmunity?

Interstitial lung disease (ILD) and lung fibrosis are characterized by different grades of fibrosis and inflammation. Persistent low-grade inflammation is believed to play a major pathogenic role, leading to an imbalance of cytokines, growth factors, and tissue proteinases. Recruited monocytes and macrophages play a pivotal role through their cytokine expression and possibly differentiation into fibrocytes, pericytes, or myofibroblasts. Atypical bacterial infections can cause ILD, although not usually in the form of usual interstitial pneumonia. On the other hand, bacterial colonization is frequently encountered in patients with chronic fibrotic lung disorders, and patients regularly undergo antibacterial treatment. As demonstrated in patients with diffuse panbronchiolitis and other chronic respiratory disorders, treatment with macrolides can be beneficial. This is partly explained by their antimicrobial effects but, for macrolides, immunomodulatory properties have been identified which might also be beneficial in patients with ILD or lung fibrosis. This article reviews the immunology of lung fibrogenesis and putative implications of macrolides for reinstallation of tolerance.