Hexachlorobenzene-induced eosinophilic and granulomatous lung inflammationis associated with in Vivo airways hyperresponsiveness in the Brown Norwayrat

We investigated whether the eosinophilic and granulomatous lung pathology t hat develops in Brown Norway (BN/SsNOlaHsd) rats upon feeding hexachloroben zene (HCB) is associated with nonspecific in vivo airways hyperresponsivene ss (AHR) to methacholine, To this end, female BN/SsNOlaHsd rats were expose d to diets with no supplementation or diets supplemented with 450 mg HCB pe r kg feed, On days 7 or 21 of exposure in vivo airways hyperresponsiveness to increasing concentrations of methacholine was assessed both by whole bod y plethysmography and by visual scoring, In addition, lungs were lavaged to count and differentiate lavage cells, and skin and lungs were processed fo r histology. Lungs of the control rats showed some scattered microgranuloma s and by 3 weeks of control diet some rats showed rather extensive granulom a formation and perivascular and peribronchiolar infiltration of eosinophil s, as well as increased responsiveness to methacholine. Oral exposure to HC B for 7 days caused a moderate perivasculitis, but no increase of total ser um IgE levels and no AHR to methacholine was found. Prolonged HCB exposure for 21 days resulted in severe and extensive eosinophilic and granulomatous lung inflammation, a threefold increase of total serum IgE levels, and mar ked cholinergic AHR in all rats. Correlation analysis revealed a significan t relation between the AHR and lung inflammation, as judged by granuloma fo rmation and increased numbers of eosinophilic granulocytes in the lung inte rstitium, particularly around the bronchi and bronchioli, No correlation wa s observed between serum IgE levels and AHR. Data suggest that HCB induces AHR by stimulating eosinophilic lung inflammation and that the preexistent microgranulomas may predispose to development of the HCB-induced lung patho logy. (C) 2001 Academic Press.