Cimetidine and the immuno-response in healthy volunteers.

We compared the immunologic measurements from treatment of 12 healthy volunteers (six male, six female) with 800 and 1,600 mg cimetidine. In the first trial 800 mg cimetidine was administered daily to the volunteers over a period of 7 d; after an interruption of 2 months, 1,600 mg of cimetidine was applied daily for 21 d. The most striking result of our study was an increased mitogen-induced lymphocyte proliferation. This conclusion can be drawn from the fact that phytohaemagglutinin (PHA) (0.4 microgram/well) and pokeweed mitogen (PWM) (0.4 microgram/well) induced lymphocyte proliferation were found to be significantly increased in comparison to pretreatment values on day 7 in both cimetidine regimens (800 mg; PHA: mean proliferation 66,500 before treatment to 166,00 cpm, PWM: mean proliferation 8,800 before treatment to 34,000 cpm; 1,600 mg; PHA; mean proliferation 48,700 before treatment to 81,600 cpm; PWM: mean proliferation 6,300 before treatment to 16,200 cpm). Increased mitogen-induced proliferation following cimetidine intake is of special interest because the mechanisms of this activation process are incompletely known. Lymphocyte proliferation response is dependent on the availability of extracellular calcium. The function of the other bivalent cations is unknown. We found that the extent of mitogen-induced lymphocyte proliferation correlates with cellular intralymphocytic zinc and magnesium amounts (coefficients of correlation [r]) (800 mg: PHA/Mg r = 0.84; PHA/Zn r = 0.86; PWM/Mg r = 0.88; PWM/Zn r = 0.87). Though the application of both cimetidine doses causes enhanced mitogen-induced lymphocyte proliferation on day 7, T lymphocytes with different phenotypic properties appear to be influenced by cimetidine. In the first dose regimen (800 mg) the number of the CD8 lymphocytes decreased significantly from 16.1% (365 cell/microliters blood) to 12.7% (264 cells/microliters blood) after 7 d of cimetidine intake. After the period of high-dose (1,600 mg) cimetidine administration (at day 21) numbers of CD4 lymphocytes were significantly increased from 41.5% (860 cells/microliters blood) to 56.3% (1,210 cells/microliters blood). Our results show that although different cimetidine doses obviously influence different cell types of healthy volunteers, the cellular mechanisms are the same, namely, a proliferation and an increased incorporation of magnesium and zinc in lymphocytes.

High dosage desferrioxamine therapy in a female patient with acquired aplastic anaemia and transfusion siderosis.

A 32 year old woman with severe aplastic anaemia required frequent transfusions and consequently developed hyperferrioxaemia (54 microMol/l) and hyperferritinaemia (1,700 ng/ml). For the treatment of transfusion siderosis she was given 18 high dose courses each comprising 35 g of desferrioxamine. Because of pre-existing thrombocytopenia (platelet count 5 X 10(9)/l) the iron chelating agent was given by continuous intravenous infusion over 3 1/2 days. High dose desferrioxamine had to be abandoned because of severe bone pain. The desferrioxamine infusions achieved a negative iron balance, iron loss after each infusion being 100 to 200 mg in the urine and 400 mg in the faeces. Serum iron and ferritin concentrations fell almost to normal. This report shows that faecal iron excretion must be taken into account in assessing the balance of iron input and output during desferrioxamine treatment.