Immunomodulatory role of ceftaroline in monocytes and macrophages.

Cigarette smoke is the principal risk factor for chronic obstructive pulmonary disease (COPD) and can negatively influence the effectiveness of the immune system's response to a pathogen. Ceftaroline is an antibiotic active against several bacterial pathogens, which has recently been identified as a drug with immune-modulatory effects in bronchial epithelial cells exposed to cigarette smoke. The present study aims to assess the effects of ceftaroline on innate immune receptors (TLR2 and TLR4) and on pro-inflammatory and defensive responses in an undifferentiated and PMA-differentiated human monocyte cell line (THP-1) exposed or not to cigarette smoke extracts (CSE). TLR2, TLR4, and LPS binding were assessed by flow cytometry, TNF-? and human beta defensin (HBD2) release were evaluated by ELISA. The constitutive expression of TLR2 and TLR4 was higher in differentiated than in undifferentiated THP-1 cells. In undifferentiated THP-1 cells, CSE increased TLR2 and TLR4 protein levels, LPS binding and TNF-? release and reduced HBD2 release. Ceftaroline counteracted the effects of CSE on TLR4 expression, LPS binding and on TNF-? and HBD2 release. In differentiated THP-1, CSE did not significantly affect TLR2 and TLR4 expression and LPS binding but reduced HBD2 release and increased TNF-? release. Ceftaroline counteracted the effects of CSE on HBD2 release in differentiated THP-1. Ceftaroline can contribute to combatting the effect of CSE in immune cells by increasing the effectiveness of the innate immune system. This effect may also assist in reducing pathogen activity and recurrent exacerbations in COPD patients.