Inhibition of pulmonary eosinophilia and airway hyperresponsiveness in allergic mice by rolipram: involvement of endogenously released corticosteroneand catecholamines
Tt. Kung et al., Inhibition of pulmonary eosinophilia and airway hyperresponsiveness in allergic mice by rolipram: involvement of endogenously released corticosteroneand catecholamines, BR J PHARM, 130(2), 2000, pp. 457-463
1 This study investigates the role of adrenal-derived catecholamines and co
rticosterone on the inhibition by rolipram, a phosphodiesterase (PDE)-4 inh
ibitor, of pulmonary eosinophilia and airway hyperresponsiveness (AHR) in a
llergic mice.
2 The following experimental groups were studied in mice sensitized and cha
llenged with ovalbumin (OVA): normal, adrenalectomized, propranolol (B-adre
noceptor antagonist) and metyrapone (corticosterone synthesis inhibitor) tr
eated. These interventions were studied both in the absence and in the pres
ence of rolipram. Eosinophil numbers in the bronchoalveolar lavage (BAL) an
d AHR to methacholine were measured 24 h after OVA challenge.
3 Treatment of sensitized mice with rolipram (0.3-10 mg kg(-1), p.o.), inhi
bited pulmonary eosinophilia and the AHR to methacholine in OVA-challenged
mice.
4 Adrenalectomy increased the number of eosinophils in the BAL of OVA-chall
enged mice but had no effect on AHR to methacholine. Adrenalectomy attenuat
ed both the rolipram-induced inhibition of BAL eosinophilia and AHR to meth
acholine in OVA challenged mice. Propranolol (10 mg kg(-1) p.o.) had no eff
ect on the inhibition of eosinophilia by rolipram but attenuated the inhibi
tion of AHR to methacholine in OVA challenged mice. On the other hand, mety
rapone (10 mg kg(-1), p.o.) attenuated the inhibition of eosinophilia by ro
lipram but had no effect on the inhibition of AHR to methacholine in OVA ch
allenged mice. Metyrapone-treatment alone increased the number of eosinophi
ls in the BAL of OVA-challenged mice.
5 These results identify an important role for adrenal-derived catecholamin
es and corticosterone on the inhibition of pulmonary eosinophilia and AHR b
y rolipram in allergic mice.