Inhibition of pulmonary eosinophilia and airway hyperresponsiveness in allergic mice by rolipram: involvement of endogenously released corticosteroneand catecholamines

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.