A role for MCP-1/CCR2 in interstitial lung disease in children

Background: Interstitial lung diseases (ILD) are chronic
inflammatory disorders leading to pulmonary fibrosis. Monocyte
chemotactic protein 1 (MCP-1) promotes collagen synthesis and
deletion of the MCP-1 receptor CCR2 protects from pulmonary
fibrosis in ILD mouse models. We hypothesized that pulmonary MCP-1
and CCR2(+) T cells accumulate in pediatric ILD and are related to
disease severity. Methods: Bronchoalveolar lavage fluid was
obtained from 25 children with ILD and 10 healthy children. Levels
of pulmonary MCP-1 and Th1/Th2-associated cytokines were quantified
at the protein and the mRNA levels. Pulmonary CCR2(+), CCR4(+),
CCR3(+), CCR5(+) and CXCR3(+) T cells were quantified by
flow-cytometry. Results: CCR2(+) T cells and MCP-1 levels were
significantly elevated in children with ILD and correlated with
forced vital capacity, total lung capacity and ILD disease severity
scores. Children with lung fibrosis had significantly higher MCP-1
levels and CCR2(+) T cells in bronchoalveolar lavage fluid compared
to non-fibrotic children. Conclusion: The results indicate that
pulmonary CCR2(+) T cells and MCP-1 contribute to the pathogenesis
of pediatric ILD and might provide a novel target for therapeutic
strategies.