In experimental studies in pigs, it was shown that the first intravenous injection of potent equine antiporcine thymocyte globulin (ATG) induced a symptomatic anaphylactic reaction which was accompanied by high plasma histamine and serotonin levels, depletion of the peripheral stores of these compounds and a pronounced lymphopenia. A refractory state followed in which further ATG injections did not induce such reactions. Patients treated with equine antihuman ATG had a similar reaction and refractory period. Antihistamine therapy was both prophylactic and effective in reversing the symptoms. It is suggested that the symptomatic anaphylactic reaction observed was due to reverse type anaphylaxis caused by an antigen antibody reaction (ATG + lymphocyte) in which pharmacological mediators were released. It was demonstrated experimentally that the refractory state was attributed to the absence of sufficient numbers of ATG sensitive lymphocytes during the subsequent injections. Depressed serum complement levels and a reduced store of histamine and serotonin observed in the experimental animals may have participated toward the induction of the refractory period. It is recommended that reverse anaphylaxis be considered when an acute reaction is observed in patients who have no evidence of antibodies to horse proteins.

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