A Microscopic Study of Inflammatory Reactions in Human Skin Induced by Histamine and Compound 48/80

Abstract

The sequential changes induced by histamine and compound 48/80 in normal skin were studied by light and electron microscopy. Histamine (50 μ g) or compound 48/80 (10 μ g) was injected intradermally as a single bolus, a repeated bolus every 15mm for 2hr. or as a constant infusion (120 μ g histamine/hr; 24 μ g compound 48/80hr) for 4hr. Skin biopsies were taken 15mm to 24hr after injection and cellular and other morphological changes were assessed in 1 μ m Epon sections by light microscopy. Fifteen minutes after a single bolus of histamine there was dilatation of dermal vessels, endothelial swelling, fibrin deposition, perivascular edema and slight mast cell degranulation. At 4hr these edema-related changes had largely regressed. Perivascular leukocytes were usually absent. After repeated bolus injections or continuous infusions of histamine a slight infiltrate of neutrophils, cosinophils and mononuclear cells was seen around venules. After a single injection of compound 48/80 there was a perivascular infiltration of neutrophils and eosinophils that was slight to moderate at 15–30mm and greater at 24hr. Electron microscopy showed that many of these leukocytes had undergone degranulation or lysis even within vessel lumina. Exocytotic mast cell degranulation was more extensive with compound 48/80 than with histamine or with phosphate buffered saline. There was marked variation in both the number of mast cells undergoing degranulation and the degree of degranulation in individual cells. We conclude that the greater cellular reaction caused by compound 48/80 probably depends upon release from mast cells of mediators other than histamine. The contribution of fibrin in acute dermal inflammation needs to be examined further.