Functional differences between human cutaneous mast cells and basophils: a comparison of morphine-induced histamine release

Abstract

Intravenous administration of morphine sulfate often produces urticarial and hypotensive reactions associated with elevations in plasma histamine. The source of this histamine and mechanisms controlling its release are poorly understood. Previous studies of morphine-induced histamine release compared human leukocytes to rat peritoneal mast cells. The effects of morphine on human cutaneous mast cells has not been examined. We studied in vitro histamine release from human basophils and human skin preparations containing cutaneous mast cells to evaluate their relative contribution to the pharmacologic effects of morphine. Human skin mast cell preparations showed dose-dependent histamine release over a morphine concentration range of 1.5 X 10(-5) to 4.5 X 10(-3) M, with peak release occurring at 5 X 10(-4) M, with peak release occurring at 5 X 10(-4) M. Clinically, morphine sulfate is usually injected as a 1.5 X 10(-2) M solution. Histamine release was calcium dependent and equivalent to that obtained with 3 and 10 mM strontium. Morphologic examination revealed degranulation and exocytosis occurring in morphine-stimulated tissue but not in specimens exposed to buffer alone. Lactate dehydrogenase levels did not increase following morphine incubation, thus supporting a noncytolytic mechanism of histamine release. Basophils, in contrast, showed no significant histamine release from exposure to morphine up to 10(-2) M. Concanavalin A, as a positive control in these same preparations, produced a mean histamine release of 21.0%.(ABSTRACT TRUNCATED AT 250 WORDS)

Opioids in Immunologic Processes

“…These effects are linked to morphine-induced elevation of plasma histamine which has been observed in both man (EBERTZ et al 1986) and animals (MULDOON et al 1984). ELLIS et al (1970) were one of the first groups to show morphine-induced histamine release from rat mast cells, an observation which has been repeated by numerous other groups.…”

“…When morphine was injected intradermally to human skin, a wheal and flare reaction was induced which was directly related to degranulation of mast cells and release of histamine (CASALE et al 1984). The effects of morphine on histamine release by skin mast cells showed calcium dependency (LIU et al 1983;EBERTZ et al 1986) and association with the inhibition of adenylate cyclase (YAMASAKI et al 1983). Interestingly, only human skin mast cells release histamine in response to morphine.…”

Morphine Modulation of the Contact Hypersensitivity Response: Characterization of Immunological Changes

“…Thus, it is plausible that the morphine-induced increase in the CHS response may involve additional inflammatory mediators or immunological alterations which occur at later time points not assessed in the present study. For example, morphine treatment has been shown to increase mast cell degranulation, potentially resulting in an increased release of histamine and a myriad of cytokines (e.g., [32][33][34][35][36]. In fact, studies have reported increased levels of histamine following antigenic challenge in previously sensitized animals (37,38).…”

Perioperative anaphylaxis

“…Opiates, including morphine, codeine and synthetic opioids such as pethidine can cause direct mast cell degranulation without the presence of specific IgE antibodies [101]. Studies have demonstrated cutaneous mast cell release of histamine after stimulation by morphine but mast cells isolated from other tissues (lung, heart, gastrointestinal) and also basophils do not [102,103]. There are rare reports of IgE antibodies to morphine and codeine being detected in patients with opiate associated anaphylaxis [104].…”