MacDermott R P, Schloemann S R, Bertovich M J, Nash G S, Peters M, Stenson W F
Department of Medicine, Barnes and Jewish Hospitals, Washington University Medical Center, St. Louis, Missouri.
Gastroenterology. 1989 Feb;96(2 Pt 1):442-8. doi: 10.1016/0016-5085(89)91569-2.
We have examined the effects of sulfasalazine and its metabolites sulfapyridine and 5-aminosalicylic acid on antibody secretion by normal peripheral blood and intestinal mononuclear cells. Sulfasalazine and 5-aminosalicylic acid both inhibited pokeweed mitogen-stimulated secretion of immunoglobulins (Igs) A, G, and M by peripheral blood mononuclear cells in a dose-dependent manner, whereas sulfapyridine had little effect. Sulfasalazine and 5-aminosalicylic acid also inhibited spontaneous secretion of IgA by intestinal mononuclear cells, but sulfapyridine did not. Sulfasalazine inhibited pokeweed mitogen-stimulated lymphocyte proliferation, while 5-aminosalicylic acid and sulfapyridine exhibited minimal inhibition. Sulfasalazine was toxic for peripheral blood mononuclear cells, whereas 5-aminosalicylic acid and sulfapyridine were not toxic. Thus, the inhibition of antibody secretion by sulfasalazine was due to direct toxicity. On the other hand, 5-aminosalicylic acid, the therapeutically active component of sulfasalazine, was neither toxic nor antiproliferative, and appeared to exert its effects on metabolic pathways directly related to antibody synthesis. The calculated ID50 values of 5-aminosalicylic acid for antibody secretion were 1.35 mM for IgA and 1.05 mM for IgG, concentrations that are achieved in the colons of treated individuals. Indomethacin did not inhibit antibody secretion at pharmacologically relevant concentrations. 5-Aminosalicylic acid mediated inhibition of antibody secretion may play a role in inflammatory bowel disease by stopping antibody-mediated memory events involved in the induction or perpetuation of the disease process.
我们研究了柳氮磺胺吡啶及其代谢产物磺胺吡啶和5-氨基水杨酸对正常外周血及肠道单核细胞抗体分泌的影响。柳氮磺胺吡啶和5-氨基水杨酸均以剂量依赖方式抑制外周血单核细胞经商陆有丝分裂原刺激后的免疫球蛋白（Ig）A、G和M的分泌，而磺胺吡啶几乎没有作用。柳氮磺胺吡啶和5-氨基水杨酸也抑制肠道单核细胞自发分泌IgA，但磺胺吡啶没有此作用。柳氮磺胺吡啶抑制经商陆有丝分裂原刺激后的淋巴细胞增殖，而5-氨基水杨酸和磺胺吡啶的抑制作用极小。柳氮磺胺吡啶对外周血单核细胞有毒性，而5-氨基水杨酸和磺胺吡啶没有毒性。因此，柳氮磺胺吡啶对抗体分泌的抑制是由于直接毒性。另一方面，柳氮磺胺吡啶的治疗活性成分5-氨基水杨酸既无毒性也无抗增殖作用，且似乎对与抗体合成直接相关的代谢途径发挥作用。计算得出5-氨基水杨酸抑制抗体分泌的半数抑制浓度（ID50）值，对IgA为1.35 mM，对IgG为1.05 mM，这些浓度在接受治疗个体的结肠中能够达到。吲哚美辛在药理学相关浓度下不抑制抗体分泌。5-氨基水杨酸介导的抗体分泌抑制可能通过阻止参与疾病过程诱导或持续的抗体介导的记忆事件，在炎症性肠病中发挥作用。
