Panush R S, Anthony C R
Clin Exp Immunol. 1976 Jan;23(1):114-25.
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.
由于人们对乙酰水杨酸（ASA）在风湿性或免疫性疾病中已知的抗炎作用机制了解甚少，我们研究了ASA对人淋巴细胞体外反应的影响。将来自正常个体的活淋巴细胞在补充有20%混合AB血浆的RPMI 1640中以10(6)个细胞/ml的浓度进行无菌培养，于37℃、5%二氧化碳条件下培养。重复培养物在添加或不添加ASA的情况下进行孵育，并分别用PHA、Con - A、PWN、念珠菌或SK - SD进行未刺激或刺激处理。在用[3H]TdR脉冲处理、收获和计数之前，培养物中单核细胞含量大于95%，活细胞含量大于80%。结果表明，向培养物中添加3 - 40mg/100ml的ASA会导致对有丝分裂原诱导的细胞增殖有显著抑制作用。低至5 - 10mg/100ml的ASA会导致约30%的[3H]TdR摄取抑制，而20mg/100ml的ASA几乎完全抑制摄取。体外这些抗原对念珠菌和SK - SD皮肤试验呈阳性的人的细胞的刺激同样被ASA抑制。在无ASA的培养基中刺激前将细胞暴露于ASA仍显示出对细胞增殖的时间和浓度依赖性抑制。正常个体在口服治疗量的ASA（血浆水平23mg/100ml）后立即以及几天后获得细胞，在无ASA的培养基中培养，与这些人在摄入ASA之前获得的细胞相比，对有丝分裂原的刺激反应较差。这些数据表明：（i）治疗浓度的ASA抑制淋巴细胞对有丝分裂原和抗原的增殖；（ii）抑制作用无细胞毒性且部分可逆；（iii）摄入治疗量ASA的正常受试者的细胞在体外对有丝分裂原的反应比摄入ASA之前差。这些观察结果与药物治疗个体的细胞免疫反应的临床研究以及ASA在免疫介导疾病中的抗炎作用的可能机制相关。
