Studies on agranulocytosis. III. The reduced glutathione (GSH) content of leukocytes of normals and patients recovered from agranulocytosis.

ITTLE is known about the reduced glutathione ( GSH ) content of leukocytes in leukopenic states. Parker and Kracke1 found a decrease in GSH of whole blood in rabbits made leukopenic and anemic by benzol. Similar data were reported by Kuzell et al.2 in a patient with agranulocytosis and anemia which followed treatment with phenylbutazone. Inasmuch as GSH is completely intracellular, it is not certain whether these low values represented development of the anemic state as opposed to a true fall in value for GSH in leukocytes. Further studies3 have shown that diets low in the sulfhydryl amino acids ( cysteine and methionine ) frequently result in a drop in the leukocyte count of experimental animals. Furthermore, the anemia and leukopenia which result from vitamin B-12 and folic acid deficiency has been associate(l with diminished GSH values in erythrocytes.4 The unusually high incidence of agranulocvtosis induced by chlorpromazine among the mentally ill, is probably a function of the large dosage of drug administered these patients.a However, the GSH index of erythrocytes of persons with psychosis was found to he lower than that observed in normals.6 A similar abnormality in leukocytes from mentally ill patients could possibly correlate with the peculiar sensitivity of this group to agranulocytosis. In view of these observations, it seemed desirable to investigate the problem of susceptibility to agranulocytosis in terms of sulfhvdryl metabolism of leukocytes. Previous studies from this laboratory7 failed to demonstrate a block in influx of sulfur#{176} labeled L-cystine and L-methionine into leukocytes of