Abstract
BackgroundNontypable Haemophilus influenzae (NTHi) is a common bacterial pathogen causing human respiratory tract infections under permissive conditions such as chronic obstructive pulmonary disease. Inhalation of β2-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 β2 agonists on the host immune response to respiratory tract infection with NTHi.MethodsMouse alveolar macrophages were stimulated in vitro with NTHi in the presence or absence of the β2 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.ResultsBoth salmeterol and salbutamol inhibited NTHi induced tumor necrosis factor-α (TNFα) release by mouse alveolar macrophages in vitro by a β receptor dependent mechanism. In line, inhalation of either salmeterol or salbutamol was associated with a reduced early TNFα production in lungs of mice infected intranasally with NTHi, an effect that was reversed by concurrent treatment with the β 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 TNFα.ConclusionThese data suggest that inhalation of salmeterol or salbutamol may negatively influence an effective clearance of NTHi from the airways.
Highlights
Nontypable Haemophilus influenzae (NTHi) is a common bacterial pathogen causing human respiratory tract infections under permissive conditions such as chronic obstructive pulmonary disease
Salmeterol and salbutamol inhibit tumor necrosis factor-α (TNFα) production by mouse alveolar macrophages stimulated with heat killed NTHi To determine whether β2 agonists inhibit TNFα release by alveolar macrophages stimulated with NTHi, MH-S cells were incubated with HKNTHi and supernatants were harvested after various time periods
Addition of 5 × 105 HKNTHi to mouse MH-S alveolar macrophages resulted in a rapid and sustained release of TNFα in culture medium reaching 13.73 ± 0.67 and 22.88 ± 2.67 ng/ ml respectively after 6 and 24 h
Summary
Nontypable Haemophilus influenzae (NTHi) is a common bacterial pathogen causing human respiratory tract infections under permissive conditions such as chronic obstructive pulmonary disease. Stimulation of β2receptors results in a number of anti-inflammatory effects, including inhibition of neutrophil activation and oxygen release, reduction of neutrophil-endothelial cell adhesion and a reduced capacity to release proinflammatory cytokines such as tumor necrosis factor (TNF)α and interleukin (IL)-1β by macrophages [5,6]. In line with these findings, we recently demonstrated that salmeterol, a long-acting β2-agonist, exerted anti-inflammatory effects in models of lipopolysaccharide (LPS)-induced lung inflammation in mice and humans, as reflected by a reduction in lung TNFα levels and an inhibition of neutrophil recruitment to the pulmonary compartment [7,8]
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