Effect of 6-Mercaptopurine on Antibody Production.

Schwartz, Robert S.; Stack, Janice; Dameshek, William

doi:10.3181/00379727-99-24281

Cited by 222 publications

(55 citation statements)

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“…Even accepting that the production of antibody to nuclear components or to cytoplasmic RNA is etiologically related ,to this disease, there is little evidence to suggest that azathioprine is effective in suppressing antibody production, other than when given simultaneously with a new antigen (1)(2)(3). Plasma cells and the long-lived lymphocytes are resistant to 6-mercaptopurine (and presumably to azathioprine) (4), and it is these cells that are probably responsible for maintaining established immunity.…”

Section: Discussionmentioning

confidence: 99%

Azathioprine in the treatment of systemic lupus erythematosus. A controlled study

Sztejnbok

Stewart

Diamond

et al. 1971

Arthritis & Rheumatism

141

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Sixteen patients with systemic lupus erythematosus have been observed for from 1 to 4 years while taking prednisone plus azathioprine in a dose of 2.5 mglkglday and compared to 19 patients with systemic lupus erythematosus managed with prednisone alone for a similar period. Patients receiving azathioprine showed a decreased mortality and morbidity, required less daily prednisone than the control group, exhibited no increased tendency to develop infection, had fewer exacerbations of their disease and maintained better renal function. Discontinuation of the azathioprine was associated with severe exacerbations of disease. The toxicity of azathioprine was minimal.Purine analogs and the cytotoxic drugs originally devised for use in neoplastic disease were soon found to have immunosuppressive activity. From this observation, clinical trials in diseases in which immunologic abnormalities are prominent inevitably followed. T h e use of both types of agents became widespread after case reports of their benefit in such diseases were published. T h e present report describes the use of one such drug, azathioprine (Imuran)', in one disease, systemic lupus erythematosus, in a controlled study. T h e study confirms the previous impressions of the usefulness of the drug in this disease, and raises questions as to the precise manner in which the drug is best employed. MATERIALS AND METHODSDuring the 3-year period, June 1966 to June 1969, patients with systemic lupus erythematosus were entered into a controlled, but nonblind study for the evaluation of azathioprine in the management of this illness. The study was performed with FDA approval and informed consent was obtained in all cases. All patients who met the following criteria were included: 1) either a positive LE cell preparation or a positive test for antinuclear antibodies (immunofluorescent technic with guinea pig liver as substrate and serum used in a 1:lO dilution); 2) objective evidence of at least two of the following manifestations of systemic lupus erythematosus: a) arthritis, b) rash, c) serositis, d) myocardi tis, e) thrombocytopenic purpura or a white blood cell count less than 3500/cu m m or hemolytic anemia, f ) renal disease as defined by an endogenous creatinine clearance of less than 75 ml/min or proteinuria greater than 0.5 g/day; and 3) no history of having received immunosuppressive or cytotoxic drugs in the past.All of the patients had positive tests for antinuclear factors. Once the diagnosis of systemic lupus

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Section: Discussionmentioning

confidence: 99%

Azathioprine in the treatment of systemic lupus erythematosus. A controlled study

Sztejnbok

Stewart

Diamond

et al. 1971

Arthritis & Rheumatism

141

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“…Administration of 6-mercaptopurine concomitantly with bovine serum albumin in rabbits has resulted in complete non-reactivity to the antigen. However, the drug had little or no effect when it was given at the height of the immune response (4). For this reason, it is believed that inhibition accompanying the use of 6-mercaptopurine and other purine analogues is concerned principally with the initial metabolic processes leading to the immune response rather than with the production or release of antibody itself.…”

Section: Inhibition Of Destruction Oe Homologous Target Cellsmentioning

confidence: 99%

Quantitative Studies on the Behavior of Sensitized Lymphocytes in Vitro

Wilson

1965

The Journal of Experimental Medicine

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On the basis of results presented in Part 1 of this series (1) it was suggested that the destructive effect of sensitized lymphocytes upon homologous cells in tissue culture depends, in part, on an active metabolism of the lymphoid cells. To provide further information on this point, the experiments to be described were conducted to ascertain whether the antimetabolite imuran, an imidazole derivative of 6-mercaptopurine, has any influence on the cytocidal and cytostatic activities of sensitized lymphoid cells against homologous target cells in vitro. Materials and MethodsThe procedures and system used to assay the destructive effect of specifically sensitized lymphoid cells on homologous target cells have been described before (1). To determine the effect of imuran on this destructive reaction, known numbers of lymphoid cells were suspended in growth medium with or without the drug and then added to Leighton tube cultures of Lewis target tumor cells of the Le-1 line. The number of these target cells remaining attached to glass at the end of a 48 hour culture period was determined with an electronic particle counter or by hemocytometer counts of cell nuclei.A stock solution of imuran 1 was prepared by dissolving 100 mg of the drug in 20 mi of sterile distilled water and raising the pH to 10 with 1 N NaOH; this solution was kept at 4"C pending use.Tre.atrncnt of the Data.--To facilitate comparisons of the data of the various experimental groups, the results are expressed as "the percentage of target cell survival"; i.e., the number of cells surviving in cultures with sensitized lymphoid cells X 100, divided by the number surviving in cultures with normal lymphoid ceils.

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“…This discovery was an important point in the development of antineoplastic and immunosuppressive agents. In 1958, the immunosuppressive activity of 6-MP in rabbits was demonstrated by Schwartz et al (1958). Shortly, 6-(1-methyl-4-nitro-5-imidazolyl) thiopurine, AZT, was synthesized by the Hitchings-Elion laboratory and shown that this analogue of 6-MP acts as a pro-drug and is reduced non-enzymatically in body to 6-MP which is converted by sensitive neoplasms to the active form 6-thioinosinate by hypoxanthine-guanine phosphoribosyl-transferase (Van Scoik et al, 1985).…”

Section: Metabolism Of Endogenous Purinesmentioning

confidence: 99%