THE EFFECT OF THE TOPICAL APPLICATION OF CORTICOTROPHIN, HYDROCORTISONE, AND FLUOROCORTISONE ON THE PROCESS OF CUTANEOUS INFLAMMATION

[摘要] A study was made of the alterations in the process of cutaneous inflam-mation effected by the topical application of hydrocortisone, fluorocortisone, and corticotrophin. The primary irritants[long dash]mustard oil and nitric acid[long dash]were used, together with erythema-inducing doses of UV rays. Five major factors influenced the results obtained in the test situations: (a) Relation between time of hormone application and induction of inflammation. Effective inhibition of inflammation resulted from the application of the hormone 2-8 hours prior to the stimulus. The maximum effect was achieved in about 6 hours. A time interval over 16 hours failed to produce any effect. If applied immediately before or after the stimulus, the hormone produced no alteration whatsoever in the majority of cases, an exacerbation of inflammation in about 1/3 of the tests, and inhibition in a few cases only. (b) Duration of contact of hormone with skin. The minimal effective contact time was one hour. Prolongation of contact time over 2 hours gave no increase in effect. (c) Concentration of hormone applied. Optimal and about equal effects were seen with concentrations of 1% hydro-cortisone, 0.25% fluorocortisone, and 5% corticotrophin. (d) Intensity of inflammatory stimulus applied. There was an inverse relationship between the intensity of the stimulus and the degree of inhibition observed in the inflammatory response. (e) Thickness of epidermis. An inverse relation was suggested between the thickness of epidermis in terms of cell layers and the hormonal effect. If the hormones were applied under optimal conditions in our experiments, complete inhibition of inflammation induced by primary irritants was observed in 75% of cases using hydrocortone and f luorocortone, and in 60% of cases using ACTH. 50% of the cases exposed to erythema-inducing doses of UV radiation failed to develop a reaction if pretreated with these same hormones. Partial inhibition was seen in the inflammatory response in a smaller number of tests. The established minimal time period of contact of hormone with skin was thought to be related to the time necessary for penetration of the hormone through skin. This explanation was supported by autoradiography. The time limits for demonstration of the effects of the hormones was thought to suggest a later destruction or loss of the hormones from the tissues tested. On the basis of these experiments, it was concluded that these hormones were capable of the inhibition of inflammation, provided that they were present in adequate concentration in the tissues at the time of application of the inflammatory stimulus. The mechanism of this action is discussed and the conclusion reached that the hormones inhibit the reaction of the cells to the primary products of inflammation. Comparable results noted with corticotrophin are described and the mechanism of this reaction discussed. This phenomenon appears to be due to an extra-adrenal effect of the trophic hormone, and the possibility is suggested that it acts directly on the target cells in its primary biochemical role.