Macrolides inhibit cytokine production by alveolar macrophages in bronchiolitis obliterans organizing pneumonia

Background: Bronchiolitis obliterans organizing pneumonia (BOOP) is a distinct clinicopathological entity histologically characterized by intra-alveolar granulation tissue and absence of extensive fibrotic lesions. Effective macrolide treatment of BOOP has been reported anecdotally.

Objectives: This study aimed to investigate whether alveolar macrophages (AMs) produce aberrant proinflammatory cytokines in BOOP and whether this can be inhibited by clarithromycin (CAM) or azithromycin (AZM).

Methods: AMs collected by bronchoalveolar lavage (BAL) from 6 BOOP patients and 8 non-ILD controls were cultured for 24 hours in the presence or absence of CAM, AZM, lipopolysaccharide (LPS), or dexamethasone (DEX). Tumor necrosis factor-α (TNF-α), soluble TNF receptor 1 (sTNFR1), sTNFR2, interleukin 1β (IL-1β), IL-6, IL-8, IL-10, interferon γ inducible protein 10 (IP-10) and CC chemokine ligand 18 (CCL18) were measured in the culture supernatant by ELISA.

Results: The spontaneous and LPS-stimulated production by AMs of all investigated cytokines was significantly increased in BOOP compared to controls. CAM and AZM induced a dose-dependent suppression of spontaneous TNF-α, sTNFR2, IL-6, IL-8 and CCL18 production (p<0.05). CAM also inhibited the IL-1β production. CAM and AZM significantly and dose-dependently attenuated the LPS-stimulated production of sTNFR1, sTNFR2, IL-8 and CCL18 (p<0.05). CAM also inhibited the LPS-stimulated TNF-α, IL-1β, IL-6 and IL-10 production.

Conclusion: Macrolides inhibit the abundant production of proinflammatory cytokines in BOOP, CAM more efficiently than AZM.