The effect of a folic acid antagonist, A-methopterin, on the level of the circulating eosinophils in humans.

With the Technical Assistance of INGA HJELT W HILE THE MECHANISM of action of the fohic acid antagonists is tsot at present clearly and fully uisderstood, there is evidence of a relationship between these drugs and the adrenal cortex. Higgiisstm observed hyperplasia of the adrenal glands with atrophy of the spleen and thymus its rats ots autopsy, followiisg the administration of A-Methopterits. Higgins and Woods2 reported that removal of the rats’ adrenal glatsds, which had etslarged with the admitsistratiots of a folic acid antagotsist, decreased the changes these drugs usually produced in the spleets, thymus, peripheral blood aisd boise marrow of normal rats. Decreased values of the uritse corticosteroids in humaiss wit-h acute leukemia, treated with Amitsopterin, were observed by Hatilots and associates and Schoetsbach atsd -co-workers.3’ Gubner et al.5 have reported recetitly that, with the admitsistratiots of Amitsopterits, there occurred remissioms of symptoms atid signs of articular and periarticular inflammatory reactiotss its rheumatoid arthritis and psoriasis. These above reports itidicate the possibility that the folic acid antagonists may act via the adrenal gland. Gubner and co-workers,5’ however, feel that the beneficial effect of Aminopterin in rheumatoid arthritis and psoriasis is not mediated by stimulatiots of I-he adretsal cortex, but probably by iishibit-iots of connective tissue reactivity with suppression of inflammatory and proliferative tissue response. The report-s of Hills, Thorn and Roche atsd their associates79 have established clearly the intimate relatiotsship betw’eets tise level of I-he circulatitig eosinophils and the activity of the adrenal cortex. A fall in the blood eosinophil level, similar to that produced with the adrenocorticotropic hormone (ACTH), was sects its the “alarm reaction” its animals following stress.mo This chatige its both cases was due apparently to a stimulat-ioms of the adretsal cortex. It is the 11-17 oxysteroid hormones of the adrenal cortex which produce, by some utsktsown mechanism, the fall in the level of the circulating blood eosinophils. Before the direct relationship betweets the 11-17 oxysteroid hormotses of the adrenal and the eosinophil level had been described, decreases its the level of the eosinophils had been reported its a variety of acute clinical conditions such as infectiotss, starvation, itsjectiomss of foreigms proteits, surgery, etc.tt_t& Observations on the eosiisophil count in man by Fisher et al.m6 showed a significant fluctuation or diurnal variation its the eosinophil coutits of fasting and non-fasting individuals.