Background: Smoking is the main cause for the development of the chronic obstructive pulmonary
disease (COPD). Bacterial pathogens (e.g. Nontypeable Haemophilus influenzae (NTHi))
are frequently found in lungs of stable COPD patients. Antibodies that specifically
block the receptor programmed death 1 (PD-1) have demonstrated efficacy as therapeutic
agents for non-small cell lung cancer.
Methods: Mice were chronically exposed to CS or NTHi and treated with an antibody targeting
PD-1 or an isotype antibody. Concentrations of PD-1 and PD-L1 were measured in serum
collected from stabile COPD patients and during acute exacerbations (AECOPD) and in
BAL fluids of stable patients.
Results: Chronic exposure of mice to CS or NTHi associated with an increased expression of
PD-1 and PD-L1 in lung tissue. Anti-PD-1 treatment decreased lung damage and neutrophilic
inflammation. PD-L1 concentrations correlated positively with PD-1 concentrations
in serum and BAL fluids. The ratio of PD-1 to PD-L1 in BAL fluids correlated with
disease severity (FEV1 predicted, GOLD III/IV).
Conclusions: The PD-1/PD-L1 axis is involved in the development of inflammation and tissue destruction
in COPD. Inflammation-induced activation of the PD-1 pathway may contribute to disease
progression.
