Seitz M, Loetscher P, Dewald B, Towbin H, Baggiolini M
Department of Rheumatology, University Hospital, Berne, Switzerland.
J Rheumatol. 1997 Aug;24(8):1471-6.
To assess the effect of various antirheumatic drugs on cytokine, cytokine inhibitor, and prostaglandin E (PGE) production by normal blood mononuclear cells (MNC) and rheumatoid arthritis (RA) synovial fibroblasts in vitro.
MNC from healthy donors and RA synovial fibroblasts were preincubated with or without prostaglandin E2 (PGE2), indomethacin, dexamethasone, gold sodium thiomalate (GSTM), methotrexate (MTX), and cyclosporin A (CyA), and then cultured in the absence or presence of interleukin-1 beta (IL-1 beta) or tumor necrosis factor-alpha (TNF-alpha) for 48 h. We characterized cytokines such as IL-1 beta, IL-8, monocyte chemoattractant protein-1 (MCP-1), and cytokine inhibitors such as IL-1 receptor antagonist (IL-1ra) and soluble TNF receptors (sTNFR p55 + p75) as well as PGE in the cell-free culture supernatants.
In MNC and synovial fibroblast cultures dexamethasone, GSTM, and PGE2 most markedly downregulated spontaneous and/or cytokine stimulated production of IL-1 beta, IL-14a, IL-8, and MCP-1, whereas sTNFR shedding was not affected. In contrast, MTX and CyA had only marginal or no effects on mediator release, whereas indomethacin inhibited only PGE production.
Among several antirheumatic drugs examined, dexamethasone and GSTM exhibited the most potent inhibitory effects on inflammatory cytokine and cytokine inhibitor production by blood mononuclear cells and synovial fibroblasts. These drugs may exert their antiinflammatory actions by unspecific suppression of monocyte and fibroblast secretory function.
评估多种抗风湿药物对正常血液单核细胞（MNC）和类风湿关节炎（RA）滑膜成纤维细胞体外细胞因子、细胞因子抑制剂及前列腺素E（PGE）产生的影响。
将来自健康供体的MNC和RA滑膜成纤维细胞，在有或无前列腺素E2（PGE2）、吲哚美辛、地塞米松、硫代苹果酸金钠（GSTM）、甲氨蝶呤（MTX）和环孢素A（CyA）的情况下进行预孵育，然后在有或无白细胞介素-1β（IL-1β）或肿瘤坏死因子-α（TNF-α）的条件下培养48小时。我们对无细胞培养上清液中的细胞因子如IL-1β、IL-8、单核细胞趋化蛋白-1（MCP-1）以及细胞因子抑制剂如IL-1受体拮抗剂（IL-1ra）和可溶性TNF受体（sTNFR p55 + p75）以及PGE进行了鉴定。
在MNC和滑膜成纤维细胞培养物中，地塞米松、GSTM和PGE2最显著地下调了IL-1β、IL-14a、IL-8和MCP-1的自发和/或细胞因子刺激产生，而sTNFR的释放未受影响。相比之下，MTX和CyA对介质释放仅有轻微影响或无影响，而吲哚美辛仅抑制PGE的产生。
在所检测的几种抗风湿药物中，地塞米松和GSTM对血液单核细胞和滑膜成纤维细胞的炎性细胞因子及细胞因子抑制剂产生表现出最有效的抑制作用。这些药物可能通过非特异性抑制单核细胞和成纤维细胞的分泌功能发挥其抗炎作用。
