Azathioprine and 6-mercaptopurine (6-MP) suppress the human mixed lymphocyte reaction (MLR) by different mechanisms.

6-MP inhibitory effects on the MLR were reversed by AIC (46%), adenine (32%), hypoxanthine (89%), adenosine (86%) and inosine (93%). AIC, adenine, hypoxanthine and inosine had no effect on azathioprine inhibition of the MLR. Adenosine at 10 microM caused 29% reversal and had no effect at 100-400 microM on azathioprine inhibition of the MLR. Reversal of 6-MP suppression of the MLR was decreased with the delay of adenosine addition. Guanine, xanthine and guanosine caused no reversal of 6-MP or azathioprine inhibitory effects on the MLR. These results show that azathioprine and 6-MP suppress the MLR by different mechanisms.

[1]  J. Maddocks,et al.  Effects of azathioprine on the human mixed lymphocyte reaction (MLR). , 1983, British journal of clinical pharmacology.

[2]  B. Osburn,et al.  The activity of purine salvage pathway enzymes in murine and horse models of congenital and acquired dysimmunity. , 1977, Developmental and comparative immunology.

[3]  R. Watts,et al.  The role of de novo purine synthesis in lymphocyte transformation. , 1977, Ciba Foundation symposium.

[4]  A. Bøyum Isolation of lymphocytes, granulocytes and macrophages. , 1976, Scandinavian journal of immunology.

[5]  J. J. Moore,et al.  Evaluation of adenosine deaminase and other purine salvage pathway enzymes in horses with combined immunodeficiency , 1976, Infection and immunity.

[6]  A. Chalmers Studies on the mechanism of formation of 5-mercapto-1-methyl-4-nitroimidazole, a metabolite of the immunosuppressive drug azathioprine. , 1974, Biochemical Pharmacology.

[7]  J. Mehrishi,et al.  Sulphydryl Groups on the Surface of Intact Ehrlich Ascites Tumour Cells, Human Blood Platelets and Lymphocytes , 1969, Nature.

[8]  J. Bach,et al.  In vitro Evaluation of Immunosuppressive Drugs , 1969, Nature.

[9]  J E Seegmiller,et al.  Kinetic studies of hypoxanthine-guanine phosphoribosyltransferase. , 1968, The Journal of biological chemistry.

[10]  A. Bøyum,et al.  Separation of leukocytes from blood and bone marrow. Introduction. , 1968 .

[11]  P. Astrup,et al.  Oxygen affinity and acid-base status of human blood during exposure to hypoxia and carbon monoxide. , 1968, Scandinavian journal of clinical and laboratory investigation. Supplementum.

[12]  Elion Gb Symposium on immunosuppressive drugs. Biochemistry and pharmacology of purine analogues. , 1967 .

[13]  Hitchings Gh Symposium on immunosuppressive drugs. Summary and concluding remarks. , 1967 .

[14]  G. Hitchings Symposium on immunosuppressive drugs. Summary and concluding remarks. , 1967, Federation proceedings.

[15]  F. Bach,et al.  One-Way Stimulation in Mixed Leukocyte Cultures , 1966, Science.

[16]  M. Hakala,et al.  PREVENTION OF THE GROWTH-INHIBITORY EFFECT OF 6-MERCAPTOPURINE BY 4-AMINOIMIDAZOLE-5-CARBOXAMIDE. , 1964, Biochimica et biophysica acta.

[17]  H. Bierman,et al.  THE CONTINUOUS FLOW SEPARATION OF LEUKOCYTES FROM HUMAN BLOOD , 1960, American Journal of the Medical Sciences.

[18]  L. Aronow,et al.  Studies on drug resistance in mammalian cells. II. 6-Mercaptopurine resistance in mouse fibroblasts. , 1960, The Journal of pharmacology and experimental therapeutics.

[19]  G. Hitchings,et al.  The purine metabolism of a 6-mercaptopurine-resistant Lactobacillus casei. , 1953, The Journal of biological chemistry.