title: Effects of acetylsalicylic acid on normal human peripheral blood lymphocytes. Inhibition of mitogen- and antigen-stimulated incorporation of tritiated thymidine.
abstract: Since mechanisms for known anti-inflammatory effects of acetylsalicylic acid (ASA) in rheumatic or immunological diseases are poorly understood, we have studied effects of ASA on in vitro responses of human lymphocytes. Viable lymphocytes from normal individuals were cultured sterilely at 10(6) cells/ml in RPMI 1640 supplemented with 20% pooled AB plasma, at 37degreesC, 5% CO2. Replicate cultures were incubated with or without adding ASA and unstimulated or stimulated by PHA, Con-A, PWN, Candida, or SK-SD. Cultures contained greater than 95% mononuclear and greater 80% viable cells before pulsing with [3H]TdR, harvesting, and counting. Results indicated that adding 3-40 mg/100 ml ASA to culture resulted in significant inhibition of mitogen-induced blastogenesis. As little as 5-10 mg/100 ml ASA caused approximately 30% inhibition of [3H]TdR uptake, and virtually complete inhibition occurred with 20 mg/100 ml of ASA. Stimulation of cells from persons who were skin-test positive for Candida and SK-SD by these antigens in vitro was similarly suppressed by ASA. Exposure of cells to ASA before stimulation in medium without ASA still demonstrated time- and concentration-dependent inhibition of blastogenesis. Cells from normal individuals, obtained immediately and several days after orally ingesting therapeutic amounts of ASA (plasma level 23 mg/100 ml), cultured in medium without ASA, stimulated less well to mitogens that did cells obtained from these persons before ASA ingestion. These data show that: (i) therapeutic concentrations of ASA inhibit lymphocyte blastogenesis to both mitogens and antigens; (ii) inhibition was non-cytotoxic and partially reversible; and (iii) cells from normal subjects who had ingested therapeutic amounts of ASA responded less well to mitogens in vitro than before ASA ingestion. These observations are pertinent to clinical investigations of cellular immune response of individuals on drug therapy and to the possible mechanism(s) of anti-inflammatory action of ASA in immunologically mediated diseases.
mesh_terms: D000946:Antigens, Fungal; D001241:Aspirin / Q000494:pharmacology*; D003208:Concanavalin A / Q000494:pharmacology; D003864:Depression, Chemical; D006801:Humans; D066298:In Vitro Techniques; D037102:Lectins / Q000494:pharmacology; D008213:Lymphocyte Activation / Q000187:drug effects*; D008214:Lymphocytes / Q000378:metabolism; D013936:Thymidine / Q000378:metabolism; D013997:Time Factors
chemical_list: D000946:Antigens, Fungal; D037102:Lectins; D003208:Concanavalin A; D001241:Aspirin; D013936:Thymidine