HEXACHLOROBENZENE-INDUCED IMMUNOMODULATION AND SKIN AND LUNG LESIONS - A COMPARISON BETWEEN BROWN-NORWAY, LEWIS, AND WISTAR RATS

Strain dependence of the induction of skin and lung lesions by hexachl orobenzene (HCB) in the rat was studied to further the insight into th e etiology of the lesions. To this end, 3- to 4-week-old female Brown Norway (BN), Lewis, and Wistar rats received diets supplemented with 1 50 mg (BN and Lewis), 450 mg (BN, Lewis, and Wistar) or 900 mg (BN and Wistar) HCB per kilogram diet for 4 weeks. Gross skin lesion developm ent during exposure as well as pathologic changes in skin and lungs an d various parameters of immunomodulation after exposure were assessed. General toxicity as judged by a slight increase in body weight gain a nd induction of liver cell hypertrophy was similar in BN and Lewis rat s exposed to 4 50 mg/kg HCB and in Wistar rats exposed to 900 mg/kg HC B. Skin lesions ranged from redness to large exudating sores with crus ts, With regard to dose, time of onset, incidence, and severity, skin lesions were very severe in BN, moderate in Lewis, and negligible in W istar. Porphyrins could not be detected in the skin, whereas porphyrin s in the liver were seen only in Lewis rats. Histology showed epiderma l hyperplasia, deep dermal venules with activated endothelium, and dee p dermal inflammatory infiltrates mainly consisting of eosinophilic gr anulocytes in BN and of mononuclear cells in Lewis and Wistar. Nonlesi onal skin of HCB-exposed rats showed very similar, though less promine nt, changes. Lung pathology appeared negligibly strain-dependent; hist ology showed venules with an activated endothelium surrounded by a per ivascular infiltrate as well as focal alveolar macrophage accumulation s in all strains. Parameters of immunomodulation showed moderate strai n dependence; relative spleen weights were dose-dependently increased in BN and Wister and in the 450 mg/kg group in Lewis rats. BN rats sho wed a more marked splenomegaly than the other strains. Relative poplit eal lymph node weights were increased significantly in BN and Lewis ra ts exposed to 450 mg/kg HCB. In all strains, HCB increased lymph node HEVs. Serum HgE and IgG levels were increased significantly in a dose- dependent way in BN rats only. Total serum IgM levels were elevated si gnificantly in BN, Lewis, and Wister rats that received 450 mg/kg and in Wister rats that received 900 mg/kg HCB. Serum IgM levels against s sDNA were dose-dependently increased in all strains, being more marked in BN and Lewis than in Wistar rats. It is concluded that the HCB-ind uced inflammatory skin and lung pathologies have different etiology. P ronounced strain differences in the skin lesions suggest a specific in volvement of the immune system. Skin lesions correlated significantly with all assessed parameters of immunomodulation in BN, with some in L ewis and with none in Wister rats. No correlation was observed between the parameters of immunomodulation and lung lesions. (C) 1997 Academi c Press.