Commentary
THE MOUSE TAIL TEST FOR EVALUATION OF TOPICALLY APPLIED CORTICOSTEROIDS R, I. C. SPEARMAN, Ph.D., AND A. JARRETT, D.Sc, F.R.C.P. (Edinb.)
From the Department of Dermatology, University College Hospital Medical School, London, England
Corticosteroids used for the topical treatment of dermatoses have several useful pharmacologic effects. Their suppression of the cellular immune response is of value in the treatment of delayed hypersensitivity reactions but it is disadvantageous in skin infections. Probably the most important effect of corticosteroids in cutaneous therapy is their stabilizing action on membranes and in particular on lysosomal membranes. This prevents the leakage of lysosomal enzymes into the cytoplasm and consequent damage or death of epidermal cells. Membrane stabilization may be basic to other pharmacologic effects of these steroids but although lysosomal stabilization can be demonstrated by both in vitro and in vivo techniques, as yet no assay method has been devised to quantitate this action on epidermal cells.'
mal penetration in hutnan skin, its value for predicting the therapeutic efficacy of a particular steroid is questionable. Two other important actions of corticosteroids are to reduce the rate of cell division,-'- ' and to decrease RNA transcription and hence the rate of protein synthesis. In consequence, the epidermis is reduced to a few cells in depth, and the cells are smaller than normal. The combined effects are helpful in the treatment of dermatoses characterized by increased epidermal mitotic activity, as for example psoriasis. The fluorinated steroids are tnuch tnore effective in the treatment of this disorder than their nonfluorinated counterparts, and this is no doubt related to the increased epidermal mitotic activity in psoriasis.
Vasoconstriction The vasoconstrictor effect of corticosteroids on dermal blood vessels, although well documented-^ and used as a test for the relative activity of different preparations, is perhaps not therapeutically significant because corticosteroids are rarely used specifically for this purpose. Thus, while it is of great value in determining the penetration of a steroid into the dermis and for deciding the relative value of different vehicles for epider-
Mouse Tail This test on the mouse tail is designed to quantitate the thinning effect of topically applied corticosteroids on the epidermis.-"^ The tail skin of the laboratory mouse (Mus muscutus) is particularly suitable for measuring small changes of epidermal thickness because the dermoepidermal junction in the scale region is almost flat and runs parallel to the skin 515
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surface. This enables accurate measurements to be made which can be evaluated statistically. The horny layer is excluded from such measurements. So far, this test has been used to compare the thinning action of commercially available corticosteroids, and the findings agree closely with assessment of these preparations for the treatment of psoriasis.^ However, this test is based on only 2 functions of these steroids, namely their repression of mitosis and their depression of protein synthesis. For disorders such as eczema, stabilization of cell membranes is probably more important. To assess a steroid for its therapeutic value in this condition, a test should be devised specifically to evaluate this action. Also, in some eczemas the action of steroids on cell-mediated immune reactions are of great importance, and again a test should be established to evaluate this facet of their action.
September 1976
Vol. 15
It is important to realize that corticosteroids have multiple pharmacologic actions. It is only by devising quantitative tests for each of these that new corticosteroids at the developmental stage can be satisfactorily evaluated. When this has been done, it may be possible in the future to produce particular steroids with the specific action for the treatment of a particular disease. References 1. Jarrett, A., Physiology and Pathophysiology of the Skin. Vol. 1. The Epidermis. London, Academic Press, 1973. 2. McKenzie, A. W., and Stoughton, R. B., Method for comparing percutaneous absorption of steroids. Arch. Dermatol. 86:608, 1962. 3. Fisher, L. B., and Maibach, H. I., The effect of corticosleroids on human epidermal mitotic activity. Arch. Dermatol. 103:39, 1971. 4. Jarrett, A., and Spearman, R. I. C, Histochemistry of the Skin, Psoriasis. London, English Universities Press, 1964, p. 36. 5. Spearman, R. I. C, and Jarrett, A., Bio-assay of corticosteroids for topical application. Br. J. Dermatol. 92:581, 1975.
Common Risk Factors Many American health problems share risk factors in common: for example, obesity, diabetes, and atherosclerosis. Interventions affecting one of these may have beneficial effects on the others as well. The largest payoffs in prevention may lie in multiple interventions in various risk factors, including the nutrition-related variables. In neither diabetes mellitus nor atherosclerosis is an approach that involves only change in nutrition (or ignores it completely) likely to lessen morbidity and mortality. The model now being used in the multiple risk-factor intervention trials (MRFIT) for the prevention of atherosclerosis—which involves aggressive treatment of obesity, attention to decreasing saturated fat and cholesterol in the diet, management of hypertension, antismoking therapy, and encouragement of a more physically active lifestyle—may have elements that are useful in preventing other conditions as well, such as diabetes mellitus—Dwyer, J. T., and Molitch, M. E.: Clinical Nutrition 1976: Where are we going? Ann. Int. Med. 84:329, 1976.
THE MOUSE TAIL TEST FOR EVALUATION OF TOPICALLY APPLIED CORTICOSTEROIDS R, I. C. SPEARMAN, Ph.D., AND A. JARRETT, D.Sc, F.R.C.P. (Edinb.)
From the Department of Dermatology, University College Hospital Medical School, London, England
Corticosteroids used for the topical treatment of dermatoses have several useful pharmacologic effects. Their suppression of the cellular immune response is of value in the treatment of delayed hypersensitivity reactions but it is disadvantageous in skin infections. Probably the most important effect of corticosteroids in cutaneous therapy is their stabilizing action on membranes and in particular on lysosomal membranes. This prevents the leakage of lysosomal enzymes into the cytoplasm and consequent damage or death of epidermal cells. Membrane stabilization may be basic to other pharmacologic effects of these steroids but although lysosomal stabilization can be demonstrated by both in vitro and in vivo techniques, as yet no assay method has been devised to quantitate this action on epidermal cells.'
mal penetration in hutnan skin, its value for predicting the therapeutic efficacy of a particular steroid is questionable. Two other important actions of corticosteroids are to reduce the rate of cell division,-'- ' and to decrease RNA transcription and hence the rate of protein synthesis. In consequence, the epidermis is reduced to a few cells in depth, and the cells are smaller than normal. The combined effects are helpful in the treatment of dermatoses characterized by increased epidermal mitotic activity, as for example psoriasis. The fluorinated steroids are tnuch tnore effective in the treatment of this disorder than their nonfluorinated counterparts, and this is no doubt related to the increased epidermal mitotic activity in psoriasis.
Vasoconstriction The vasoconstrictor effect of corticosteroids on dermal blood vessels, although well documented-^ and used as a test for the relative activity of different preparations, is perhaps not therapeutically significant because corticosteroids are rarely used specifically for this purpose. Thus, while it is of great value in determining the penetration of a steroid into the dermis and for deciding the relative value of different vehicles for epider-
Mouse Tail This test on the mouse tail is designed to quantitate the thinning effect of topically applied corticosteroids on the epidermis.-"^ The tail skin of the laboratory mouse (Mus muscutus) is particularly suitable for measuring small changes of epidermal thickness because the dermoepidermal junction in the scale region is almost flat and runs parallel to the skin 515
516
INTERNATIONAL JOURNAL OF DERMATOLOGY
surface. This enables accurate measurements to be made which can be evaluated statistically. The horny layer is excluded from such measurements. So far, this test has been used to compare the thinning action of commercially available corticosteroids, and the findings agree closely with assessment of these preparations for the treatment of psoriasis.^ However, this test is based on only 2 functions of these steroids, namely their repression of mitosis and their depression of protein synthesis. For disorders such as eczema, stabilization of cell membranes is probably more important. To assess a steroid for its therapeutic value in this condition, a test should be devised specifically to evaluate this action. Also, in some eczemas the action of steroids on cell-mediated immune reactions are of great importance, and again a test should be established to evaluate this facet of their action.
September 1976
Vol. 15
It is important to realize that corticosteroids have multiple pharmacologic actions. It is only by devising quantitative tests for each of these that new corticosteroids at the developmental stage can be satisfactorily evaluated. When this has been done, it may be possible in the future to produce particular steroids with the specific action for the treatment of a particular disease. References 1. Jarrett, A., Physiology and Pathophysiology of the Skin. Vol. 1. The Epidermis. London, Academic Press, 1973. 2. McKenzie, A. W., and Stoughton, R. B., Method for comparing percutaneous absorption of steroids. Arch. Dermatol. 86:608, 1962. 3. Fisher, L. B., and Maibach, H. I., The effect of corticosleroids on human epidermal mitotic activity. Arch. Dermatol. 103:39, 1971. 4. Jarrett, A., and Spearman, R. I. C, Histochemistry of the Skin, Psoriasis. London, English Universities Press, 1964, p. 36. 5. Spearman, R. I. C, and Jarrett, A., Bio-assay of corticosteroids for topical application. Br. J. Dermatol. 92:581, 1975.
Common Risk Factors Many American health problems share risk factors in common: for example, obesity, diabetes, and atherosclerosis. Interventions affecting one of these may have beneficial effects on the others as well. The largest payoffs in prevention may lie in multiple interventions in various risk factors, including the nutrition-related variables. In neither diabetes mellitus nor atherosclerosis is an approach that involves only change in nutrition (or ignores it completely) likely to lessen morbidity and mortality. The model now being used in the multiple risk-factor intervention trials (MRFIT) for the prevention of atherosclerosis—which involves aggressive treatment of obesity, attention to decreasing saturated fat and cholesterol in the diet, management of hypertension, antismoking therapy, and encouragement of a more physically active lifestyle—may have elements that are useful in preventing other conditions as well, such as diabetes mellitus—Dwyer, J. T., and Molitch, M. E.: Clinical Nutrition 1976: Where are we going? Ann. Int. Med. 84:329, 1976.
