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B ackground CC chemokine ligand (CCL)5 and its receptor CCR5 contribute to leukocyte migration into lungs of patients with diffuse lung diseases (DLD). Pharmacological regulation of CCL5 and CCR5 expression was therefore explored in bronchoalveolar cells obtained from patients with DLD. Methods Cells from 21 patients were co-cultivated in vitro with tumour necrosis factor-α and dexamethasone, cyclosporin A (CyA) or pentoxifylline. Chemokine mRNA expression and protein production was assessed by reverse transcription-polymerase chain reaction and enzyme-linked immunosorbent assay, respectively. Results Dexamethasone altered CCL5 mRNA expression and suppressed its protein levels. CyA inhibited chemokine mRNA expression but not protein production. Pentoxifylline did not affected chemokine expression. Both dexamethasone and CyA suppressed CCR5 mRNA transcripts. Conclusion In conclusion, while dexamethasone downregulates the CCL5 functional form, CyA and pentoxifylline have no effects on CCL5 protein. These data provide in vitro correlation for clinical applications of immunomodulators in therapy of DLD. [ABSTRACT FROM AUTHOR]

The CC chemokine receptor 5 (CCR5) binds the chemokine ligands RANTES (CCL5) and MIP-1α (CCL3), which have been implicated in the development of alveolitis in sarcoidosis. We have, therefore, investigated CCR5 mRNA expression in bronchoalveolar lavage fluid (BALF) cells from patients with sarcoidosis. Further, we explored whether there was any association between CCR5 mRNA expression and the presence of the CCR5Δ32 DNA polymorphism. Semiquantitative RT-PCR was used to determine CCR5 mRNA expression from BALF cells from 16 control subjects (C) and 39 patients with sarcoidosis (S). The data on the CCR5Δ32 polymorphism, determined by PCR-SSP, were available for 37 patients. CCR5 mRNA expression was significantly upregulated in sarcoidosis (median±SEM, C, 0.00±0.07; S, 0.12±0.07; P<0.05). When patients were evaluated according to their CCR5Δ32 genotype, an interesting trend emerged with Δ32 positive patients (wt, mt) expressing less mRNA than the patients with both wild-type alleles (wt, wt): 0.00±0.09, and 0.26±0.09, respectively; P>0.05). In conclusion, upregulation of CCR5 mRNA in BALF of patients with sarcoidosis is consistent with its chemokine ligands RANTES and MIP-1α playing a pivotal role in inflammatory cell recruitment to disease sites. Though the data from this pilot study had no clinical correlations we suggest that further studies are warranted on the role of this Th1 subset marker in the pathogenesis of sarcoidosis. [Copyright &y& Elsevier]