Differential effects of budesonide and fluticasone propionate on bacterial recognition receptors in COPD macrophages

Abstract

Rationale: COPD patients have a high risk of community-acquired pneumonia (CAP). We studied Streptococcus pneumoniae (SP) and non-typeable Haemophilus influenzae (NTHI) effects on COPD macrophage responses and how budesonide (BUD) and fluticasone propionate (FP) alter host-pathogen interactions. Methods: Blood monocytes from 10 controls, 20 healthy smokers and moderate-severe COPD [19 current smokers (CS), 21 ex-smokers (ES)] were cultured with GM-CSF to generate monocyte-derived macrophages (MDM). MDM were pre-treated with 10nM BUD, FP or vehicle for 24h and exposed to live SP or NTHI. After 24h cell surface bacterial recognition receptor expression was analyzed by flow cytometry and supernatant cytokines by bead array. Data at p≤0.05 (2-sided paired t-test) are shown. Results: SP and NTHI reduced receptor expression on MDM from COPD (mainly in ES) and healthy smokers but not controls. SP and NTHI reduced SRA-1 in CS & ES and MARCO in ES. SP also reduced CD1d, TLR2 and TLR4 in CS & ES and CD93 in ES. NTHI also reduced CD11b in CS & ES and CD35 and CD206 in ES. BUD prevented reductions by SP on SRA-1 and by NTHI on CD206, both in ES. FP prevented SP reductions of TLR2 in CS & ES and TLR4 in ES but had no effect on reductions by NTHI. BUD and FP inhibited NTHI- and SP-induced cytokines. Conclusions: Reduction of bacterial recognition receptors on macrophages may be part of the enhanced risk of CAP in COPD. BUD prevented receptor reductions induced in ex-smokers by both SP and NTHI while FP affected only SP-induced reductions. These differential effects may contribute to the difference in pneumonia risk between inhaled BUD and FP treatments in COPD. Support: AstraZeneca.