DETERMINATION OF N-METHYLHISTAMINE IN URINE AS AN INDICATOR OF HISTAMINE-RELEASE IN IMMEDIATE ALLERGIC REACTIONS

The use of urine histamine metabolite, N-methylhistamine (N-MH), as a parameter of histamine release in immediate allergic reactions was investigated. Baseline levels were determined in 34 normal control subjects and 29 atopic patients. Increases of urine N-MH values were measured during histamine infusions and in venom-allergic patients receiving bee-sting challenges. N-MH was determined by a newly developed radioimmunoassay. Baseline levels in control subjects and atopic patients demonstrated no significant differences. With regard to challenge tests, fluctuation of N-MH levels during a 6-hour period was measured. Random 6-hour increases in health and atopic subjects ranged from 5% to 41%. Before infusion of histamine (0.25-mu-g/kg/min for 30 minutes), baseline values were 137 +/- 11.4-mu-g N-MH per gram of creatinine and 9 +/- 1.1-mu-g N-MH per hour (n = 9). Levels peaked 1 hour after infusion at 275 +/- 45-mu-g/gm of creatinine and 44 +/- 5.6-mu-g/hr and decreased to resting levels after 2 hours. Metabolization by N-MH accounted for 9.5% +/- 4.9% (range, 2.4% to 18.4%) of infused histamine in the urine of the nine subjects. Bee-sting challenges were performed in 12 patients and three control subjects. Only in three patients experiencing generalized urticaria, nausea, dyspnea, and hypotension were significant increases of urine N-MH levels (138%, 144%, and 238%) observed. All other patients and three normal control subjects demonstrated normal local reactions without increase of N-MH values. Thus, excretion of N-MH in urine reflected increased histaminemia in histamine infusions and provided a useful index of histamine release into the circulation in patients exhibiting immediate allergic reactions after bee-sting challenges. Easy accessibility, the possibility of retrospective analysis, and the high metabolization rate of histamine to N-MH suggest the use of this parameter for evaluation of histamine release in humans.