Effects of Corticosteroid on Histamine Degrading-enzyme Activities in Skin and Kidney of MRL/l Mice

In order to clarify the pathogenesis of lupus dermatoses and lupus nephritis, histamine degrading-enzyme activities in the skin and the kidney of MRL/Mp-lpr/lpr (MRL/l) mice were investigated, since the mice with lupus nephritis are the most attractive among several murine models from a dermatopathological point of view because their skin lesions resemble very well to those of human SLE. In the dorsal lesional skin of MRL/l mice, the specific activity of histamine-N-methyltransferase (HMT), the major histamine metabolizing enzyme in murine skin and kidney, was markedly lower than that in abdominal uninvolved skin. In addition, age-related analysis of HMT activity in the dorsal skin of MRL/l mice revealed that the activity increased by age and was maximum at 1 or 2 months, and then decreased at 4 or 5 months when skin lesion appeared. However, HMT activity of the abdominal skin increased almost linearly by age. In contrast, histamine degrading-enzyme activity in kidney of MRL/l mice increased almost linearly by age. There were no differences between the HMT activities of perfused kidney and non-perfused one. Whole blood and serum had little enzyme activities. In vivo administration of corticosteroid (betamethasone) restored the HMT activity in the dorsal lesional skin of MRL/l mice, although no significant macroscopic or histological differences were present in skin lesion of corticosteroid-treated mice when compared with non-treated mice. However, in vivo administration of corticosteroid had no significant effect on the enzyme activities of the kidney. Corticosteroid did not recover the HMT activity when added directly to the enzyme preparation obtained from the skin lesion. Based on these findings, the effects of released histamine at least in the lesional skin of MRL/l mice are considered to last much longer than in the normal skin, which may contribute significantly to the development of the lupus dermatoses.