Inhalation of β2 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 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. METHODS: Mouse 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. RESULTS: Both 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. CONCLUSION: These data suggest that inhalation of salmeterol or salbutamol may negatively influence an effective clearance of NTHi from the airways

Effects of cyclosporin A on rat osteoblasts (ROS 17/2.8 cells) in vitro

The effects of the immunosuppressive drug cyclosporin A (CsA) were evaluated on ROS 17/2.8 cells in vitro . ROS cells were treated with CsA (0, 0.5, 1.0, 5.0 μg/ml) for 3 days with and without bovine parathyroid hormone (bPTH) (1–34) 10 nM. CsA at 0.5, 1.0, 5.0 μg/ml without PTH and at 5.0 μg/ml in the presence of PTH significantly inhibited proliferation, as determined by a tetrazolium colorimetric assay. In addition, ROS cell number was significantly reduced at 3 and 4 days with CsA (5.0 μg/ml) without affecting cell viability. Incorporation of [ 3 H]-thymidine into DNA was significantly reduced by 3.0 and 5.0 μg/ml CsA after 12 and 24 hours exposure. Basal and 1,25-dihydroxyvitamin D 3 -stimulated alkaline phosphatase levels in confluent ROS cells were reduced ( P <0.05) with CsA (1.0 and 3.0 μg/ml). Pretreatment of ROS 17/2.8 cells with CsA did not alter PTH-stimulated cAMP levels or [ 125 I]-PTHrP binding to ROS cells. CsA treatment of ROS 17/2.8 cells induced a spindle-shaped appearance with loss of attachment in confluent cultures. When ROS cells were cultured in CsA-containing media, cellular attachment at 6 and 12 hours was reduced ( P <0.05) compared with untreated ROS cells. These findings indicate that CsA was capable of inhibiting proliferation, cell number, mitogenesis, alkaline phosphatase levels, and cell attachment of ROS cells without affecting PTH binding or cAMP levels. This direct effect of CsA on osteoblasts may be important in changes of bone remodeling observed in CsA-treated humans and animals.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/48004/1/223_2004_Article_BF00334490.pd