Role of Mast Cells, Basophils and Their Mediators in Adverse Reactions to General Anesthetics and Radiocontrast Media

Abstract

General anesthetics and radiocontrast media (RCM) can cause anaphylactic or anaphylactoid reactions. These are usually underdiagnosed and underreported, but their incidence is apparently rising. Their pathogenesis is complex and not completely understood, but the release of vasoactive mediators from basophils and mast cells plays a central role. The recent development of in vitro techniques to study the release of preformed (histamine and tryptase) and de novo synthesized mediators (PGD₂, LTC₄, and PAF) from purified basophils and mast cells has made it possible to quantify the mediator-releasing activity of anesthetics such as muscle relaxants, general anesthetics, opioids, and benzodiazepines and RCM on human basophils and mast cells isolated from lung, skin and heart tissues. The majority of general anesthetics and RCM tested induced only the release of preformed mediators (histamine and tryptase), not of the de novo synthesized eicosanoids. There was wide variability in the response of basophils and mast cells from different donors to the same drug or RCM, presumably due to the releasability parameter. Hyperosmolality is probably not the only factor responsible for basophil and mast cell activation by RCM. The in vitro release of histamine induced by anesthetic drugs and RCM was correlated with the release of tryptase. Given the longer half-life of tryptase than histamine in plasma, measurements of plasma tryptase may become a useful diagnostic tool for identifying adverse reactions to anesthetics and RCM.

Delayed allergy-like reactions to X-ray contrast media: mechanistic considerations

“…This statement is based on in vitro studies, which have shown that histamine is released from human basophils in the presence of high concentrations of X-ray CM. There are no in vivo results which indicate that the delayed cutaneous eruptions to nonionic CM are caused by direct release of histamine from skin mast cells [90]. Such a mechanism would be concentration dependent and result in an immediate reaction.…”

Clinical consequences of mast cell heterogeneity

“…The poor in vitro response of skin mast cells to RCM suggests that these reactions involves complement activation and anaphylatoxin formation that may trigger skin mast cell degranulation in vivo [47,50,60].…”

“…Studies have demonstrated that hyperosmolarity may be more important in inducing histamine release from basophils than from mast cells as a correlation between histamine release and osmolarity is apparent in basophils but not in mast cells [57,60]. Indeed while agents of low osmolarity Hexabrix and Optipray have been demonstrated to induce concentration dependent histamine release from human lung parenchymal mast cells; Telebrix, a high osmolarity RCM which activates basophils, did not induce histamine release from human lung mast cells [57,60].…”

“…Indeed while agents of low osmolarity Hexabrix and Optipray have been demonstrated to induce concentration dependent histamine release from human lung parenchymal mast cells; Telebrix, a high osmolarity RCM which activates basophils, did not induce histamine release from human lung mast cells [57,60]. The effects of the RCM Iohexal and Urographin have been assessed in basophils and BAL mast cells from the same donors [61].…”

“…In contrast to morphine, buprenorphine causes histamine and tryptase release from lung but not from skin mast cells. Further, buprenorphine induces the de novo synthesis of PGD 2 and LTC 4 from lung mast cells while morphine acts an incomplete secretagogue on skin mast cells, with the response limited to the release of preformed mediators [60,74]. The synthetic phenyl piperidine, fentanyl does not induce mediator release from isolated skin, heart and lung mast cells or human basophils [75].…”