Effect of pyrimethamine and sulphadoxine on human lymphocyte proliferation

TY - JOUR

T1 - Effect of pyrimethamine and sulphadoxine on human lymphocyte proliferation

AU - Bygbjerg, I C

AU - Odum, Niels

AU - Theander, T G

N1 - Keywords: Cell Survival; DNA; Humans; Leukocyte Count; Lymphocyte Activation; Lymphocytes; Mitosis; Phytohemagglutinins; Pokeweed Mitogens; Pyrimethamine; Sulfadoxine; Sulfanilamides; Thymidine; Tuberculin

PY - 1986

Y1 - 1986

N2 - The in vitro effect of pyrimethamine (PYR) on human blood mononuclear cells stimulated with phytohaemagglutinin (PHA), pokeweed mitogen (PWM) and purified protein derivative of tuberculin (PPD) was studied by 14C-thymidine incorporation, by cell counting and by total DNA estimation. PYR in concentrations 10 times higher than serum values obtained in clinical practice inhibited lymphocyte proliferation irreversibly. PYR in concentrations corresponding to clinical practice quickly and irreversibly suppressed the proliferation of PWM-stimulated cells, and more slowly the proliferation of PPD-stimulated cells. The suppression of PHA-stimulated cells was reversed after one week. The increased 14C-thymidine incorporation observed in stimulated cells exposed to PYR in vitro in the early phase of proliferation did not reflect immunopotentiation but rather blocked endogenous thymidine synthesis. Sulphadoxine (SDX), added in vitro, had no effect on the lymphocytes, while SDX plus PYR had the same effect as PYR alone. Oral intake of SDX plus PYR (Fansidar) also blocked the thymidine synthesis of mitogen-stimulated lymphocytes. The possible consequences of the findings for the use of PYR in malaria prophylaxis and therapy are discussed.

AB - The in vitro effect of pyrimethamine (PYR) on human blood mononuclear cells stimulated with phytohaemagglutinin (PHA), pokeweed mitogen (PWM) and purified protein derivative of tuberculin (PPD) was studied by 14C-thymidine incorporation, by cell counting and by total DNA estimation. PYR in concentrations 10 times higher than serum values obtained in clinical practice inhibited lymphocyte proliferation irreversibly. PYR in concentrations corresponding to clinical practice quickly and irreversibly suppressed the proliferation of PWM-stimulated cells, and more slowly the proliferation of PPD-stimulated cells. The suppression of PHA-stimulated cells was reversed after one week. The increased 14C-thymidine incorporation observed in stimulated cells exposed to PYR in vitro in the early phase of proliferation did not reflect immunopotentiation but rather blocked endogenous thymidine synthesis. Sulphadoxine (SDX), added in vitro, had no effect on the lymphocytes, while SDX plus PYR had the same effect as PYR alone. Oral intake of SDX plus PYR (Fansidar) also blocked the thymidine synthesis of mitogen-stimulated lymphocytes. The possible consequences of the findings for the use of PYR in malaria prophylaxis and therapy are discussed.

M3 - Journal article

C2 - 3787690

SN - 0035-9203

VL - 80

SP - 295

EP - 300

JO - Transactions of the Royal Society of Tropical Medicine and Hygiene

JF - Transactions of the Royal Society of Tropical Medicine and Hygiene

IS - 2

ER -