Intestinal diamine oxidases and enteral-induced histaminosis: studies on three prognostic variables in an epidemiological model.

The danger of luminal histamine administered orally or formed in the intestinal fluid by bacteria has long been neglected. However, the demonstration of blocking intestinal diamine oxidase (DAO) by a variety of common drugs has revived the discussion and has created a new disease concept: enteral-induced histaminosis. In an animal model the three central prognostic variables of this disease concept (large amounts of histamine in food to make the individual ill, blocking of DAO by commonly used drugs, and the relationship between increased plasma histamine levels and disease manifestation by exogenous histamine application) were tested with randomized trials in vivo and biochemical tests in vitro using semipurified enzymes from pig and man. In the first trials authentic histamine in quantities similar to that in normal amounts of food or cheese bought from a supermarket produced life-threatening reactions if the DAO was inhibited by pretreatment with aminoguanidine. In the second series of experiments in vitro a numerous commonly used drugs was shown to inhibit both the porcine and human enzyme. Some of the inhibitors were really strong, such as dihydralazine, chloroquine, pentamidine, cycloserine, clavulanic acid, dobutamine, pancuronium and others. The type of inhibition was sometimes competitive as in the case of dihydralazine and pancuronium, sometimes non competitive (e.g. pentamidine) which may be important for long-term treatment. In the third group of experiments a relationship between the dose of i.v. injected histamine and the elevation in plasma histamine levels and clinical symptoms in pigs was demonstrated. Hence, elevated plasma histamine in pigs acts as a pathogenetic factor for the disease manifestation. It is concluded that after modelling enteral-induced histaminosis in an animal the trias of variables shown in this study should be consequently investigated in man.