Inhalation of beta 2 agonists impairs the clearance of nontypable Haemophilus influenzae from the murine respiratory tract.
BACKGROUND
Nontypable Haemophilus influenzae (NTHi) is a common bacterial pathogen causing human respiratory tract infections under permissive conditions such as chronic obstructive pulmonary disease. Inhalation of beta2-receptor agonists is a widely used treatment in patients with chronic obstructive pulmonary disease. The aim of this study was to determine the effect of inhalation of beta2 agonists on the host immune response to respiratory tract infection with NTHi.


METHODS
Mouse alveolar macrophages were stimulated in vitro with NTHi in the presence or absence of the beta2 receptor agonists salmeterol or salbutamol. In addition, mice received salmeterol or salbutamol by inhalation and were intranasally infected with NTHi. End points were pulmonary inflammation and bacterial loads.


RESULTS
Both salmeterol and salbutamol inhibited NTHi induced tumor necrosis factor-alpha (TNFalpha) release by mouse alveolar macrophages in vitro by a beta receptor dependent mechanism. In line, inhalation of either salmeterol or salbutamol was associated with a reduced early TNFalpha production in lungs of mice infected intranasally with NTHi, an effect that was reversed by concurrent treatment with the beta blocker propranolol. The clearance of NTHi from the lungs was impaired in mice treated with salmeterol or salbutamol, an adverse effect that was prevented by propranolol and independent of the reduction in TNFalpha.


CONCLUSIONS
These data suggest that inhalation of salmeterol or salbutamol may negatively influence an effective clearance of NTHi from the airways.
Maris
Nico A
NA
Center of Infection and Immunity Amsterdam (CINIMA), Academic Medical Center, University of Amsterdam, Amsterdam, The Netherlands. namaris@yahoo.com
Florquin
Sandrine
S
van't Veer
Cornelis
C
de Vos
Alex F
AF
Buurman
Wim
W
Jansen
Henk M
HM
van der Poll
Tom
T
D000280:Administration, Inhalation; D058666:Adrenergic beta-2 Receptor Agonists; D000318:Adrenergic beta-Agonists / Q000008:administration & dosage*; D000818:Animals; D005260:Female; D006192:Haemophilus Infections / Q000378:metabolism; D006193:Haemophilus influenzae / Q000145:classification* / Q000187:drug effects*; D016676:Macrophages, Alveolar / Q000187:drug effects / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D018343:Receptors, Adrenergic, beta-2 / Q000378:metabolism; D012137:Respiratory System / Q000187:drug effects* / Q000378:metabolism
D058666:Adrenergic beta-2 Receptor Agonists; D000318:Adrenergic beta-Agonists; D018343:Receptors, Adrenergic, beta-2