The effect of salicylate on the metabolism of normal and stimulated human lymphocytes in vitro.

The effect of salicylate on the metabolism of peripheral blood lymphocytes in tissue culture was investigated. Lymphocytes incubated with sodium salicylate at a concentration of 30 mg/100 ml showed increased glucose consumption, lactic acid production, and oxygen consumption, evidence for uncoupling of oxidative phosphorylation. No decrease in cell number or viability (trypan blue dye exclusion) was noted in salicylate-treated cultures. Normal DNA, RNA, and total protein synthesis measured by radioisotope incorporation was depressed in the salicylate-treated cultures. Increased DNA synthesis after the addition of a mitogen (PHA) or antigen (PPD) to the culture was strikingly suppressed by salicylate. The degree of suppression was proportional to the concentration of salicylate used. The effect on RNA and protein synthesis in stimulated lymphocytes was much less pronounced. Acetylsalicylic acid was found to be as active as sodium salicylate in suppressing DNA synthesis, but the p-OH congener (p-OH benzoic acid) did not alter cell respiration, glycolysis, viability, or DNA synthesis. The salicylate effect was reversible as evidenced by return of cellular reactivity upon removal of the drug from the media.