Background: Chemotactic cytokines (chemokines) have been recently implicated in the pathogenesis of interstitial lung diseases. A novel chemokine called pulmonary and activation-regulated chemokine (PARC/CCL18), which attracts lymphocytes in vitro, has been detected in the human lung. We have, therefore, investigated PARC mRNA expression in bronchoalveolar lavage fluid (BALF) cells of patients with pulmonary sarcoidosis-a disease characterised by a lymphocytic infiltrate. Further, because several immunomodulators are used in the treatment of sarcoidosis, we have determined the effects of selected drugs on PARC mRNA expression in vitro.
Subjects and methods: BALF cells were obtained by standard bronchoalveolar lavage (BAL) from 30 patients with pulmonary sarcoidosis (S) and 16 control subjects (C). BALF cells from seven subjects were cultured in the presence of dexamethasone (Dx), cyclosporin A (CyA) and pentoxifylline (Px). PARC mRNA expression was semiquantitated by reverse-transcription polymerase chain reaction (RT-PCR) using normalisation to the expression of the beta-actin gene.
Results: PARC mRNA transcripts were detected in 87% of all investigated BALF samples. The expression (ODR PARC/beta-actin; median, the first to the third quartile range) was similar in both groups tested (S, 0.60 (0.50-0.95); C, 0.59 (0.36-0.93); S vs. C: P>0.05). PARC mRNA expression was not associated with the number of lymphocytes in bronchoalveolar space. PARC mRNA expression was significantly suppressed by Dx (P=0.02); CyA and Px showed a moderate inhibitory effect which did not attain significance.
Conclusion: mRNA for the chemokine PARC is expressed in the lower respiratory tract in both healthy subjects and patients with pulmonary sarcoidosis. Out of the three immunomodulatory drugs tested, Dx downregulates PARC mRNA expression in BALF cells in vitro.