Studies of desensitization and cross-desensitization to immunologic and nonimmunologic stimuli that evoke contraction and histamine release in superfused guinea pig trachea.

This study examined the possibility that there is cross-desensitization between immunologic and nonimmunologic stimuli that evoke contraction and histamine release (HR) in the isolated guinea pig trachea. Compound 48/80 and D-tubocurarine were found to cause homologous and heterologous desensitization for both contraction and HR from superfused trachea. Specific antigen challenge of trachea obtained from animals sensitized with either IgG1 (ovalbumin [OA]) or IgE (oxazalone-human serum albumin [OX-HSA]) also resulted in homologous desensitization for both contraction and HR. However, in experiments with animals sensitized with both IgG1 and IgE antibodies, prechallenge with OA resulted in cross-desensitization to OX-HSA, whereas the reverse sequence was ineffective in eliciting this phenomenon. This may be related to the type of desensitization produced by each antigen (specific versus nonspecific) or to heterogeneity of mast cells in the tissue. Prechallenge of the trachea with compound 48/80 or D-tubocurarine failed to alter subsequent effects of antigen after active sensitization with OA or passive sensitization with either IgG1 or IgE antibodies. Small but statistically significant decreases in tracheal responses to D-tubocurarine were observed after antigen prechallenge to active both IgG1 and IgE antibodies. This is the first study to demonstrate a cross-desensitization between compound 48/80 and D-tubocurarine and the first to examine cross-desensitization with IgG1 and IgE antibodies in the guinea pig trachea. The overall conclusion is that there is no major overlap in the desensitization mechanisms between immunologic and nonimmunologic stimuli in the guinea pig trachea.

Cross-reactivity of metocurine, atracurium, vecuronium and fazadinium with IgE antibodies from patients unexposed to these drugs but allergic to other myoneural blocking drugs.

An inhibition assay was used to determine quantitatively the allergenic cross-reactivity of some myoneural blocking drugs not yet released for use in Australia, in the sera of patients who had experienced anaphylactic reactions to neuromuscular blocking drugs. Two of the compounds, metocurine and atracurium were highly cross-reactive with the currently used myoneural blockers; fazadinium was weakly cross-reactive and vecuronium intermediate in potency between these two extremes. From these results, we predict that anaphylactic reactions to these compounds, and particularly to metocurine and atracurium, will occur in some patients allergic to the currently used neuromuscular blocking agents.

Positive intradermal tests to D-tubocurarine in patients with cholinergic urticaria.

Patients with cholinergic urticaria exhibit increased hypersensitivity to cholinergic drugs. In the present study, an attempt was made to determine whether these patients would also cross-react to various neuromuscular blocking agents having structures analogous with acetylcholine. The four patients tested showed positive skin tests for D-tubocurarine at concentrations of 1/10,000. None of the 10 subjects in the control group and none of the patients with urticaria had positive responses, not even to a 10-fold higher concentration of D-tubocurarine. These findings suggest that caution should be exercised in the use of neuromuscular blocking agents in patients with cholinergic urticaria.

Detection of serum IgE antibodies that react with alcuronium and tubocurarine after life-threatening reactions to muscle-relaxant drugs.

Although anaphylactoid reactions to muscle-relaxant drugs are now well recognised, there has been no general agreement on the mechanism(s) underlying the responses. By covalently coupling alcuronium and tubocurarine to a solid phase carrier and using the resultant complexes in radioimmunoassay experiments with patients' sera and 125I-anti-human IgE, we have found high levels of drug-specific IgE antibodies in the sera of some subjects who reacted to these muscle relaxants. These results provide important supporting evidence that, in some patients at least, life-threatening anaphylactoid reactions to muscle-relaxant drugs are mediated by drug-specific IgE antibodies.