Dechanet J, Taupin J L, Chomarat P, Rissoan M C, Moreau J F, Banchereau J, Miossec P
Schering-Plough Laboratory for Immunological Research, Dardilly, France.
Eur J Immunol. 1994 Dec;24(12):3222-8. doi: 10.1002/eji.1830241247.
The expression of the proinflammatory cytokine leukemia inhibitory factor (LIF) has been reported in the cartilage and synovium of rheumatoid arthritis (RA) patients. Here, we show that high levels of LIF were constitutively produced by cultures of synovium pieces. Low levels of LIF were produced spontaneously by isolated synoviocytes, but interleukin (IL)-1 beta caused a fourfold enhancement of this secretion. The anti-inflammatory cytokine IL-4 reduced the production of LIF by synovium pieces by 75%, as observed earlier with IL-6, IL-1 beta and tumor necrosis factor (TNF)-alpha. IL-4 had a direct effect since it inhibited LIF production by unstimulated and IL-1 beta- or TNF-alpha-stimulated synoviocytes. Conversely, IL-4 enhanced the production of IL-6, which shares with LIF biological activities and receptor components. The inhibitory effect of IL-4 was dose dependent and was reversed using a blocking anti-IL-4 receptor antibody. Similar inhibitory action of IL-4 on LIF production was observed on synovium pieces from patients with osteoarthritis and on normal synoviocytes. IL-10, another anti-inflammatory cytokine acting on monocytes, had no effect on LIF production by either synovium pieces or isolated synoviocytes. Thus, the production of LIF by synovium tissue was inhibited by IL-4 through both a direct effect on synoviocytes and an indirect effect by inhibition of the production of LIF-inducing cytokines.
促炎细胞因子白血病抑制因子（LIF）在类风湿关节炎（RA）患者的软骨和滑膜中的表达已有报道。在此，我们发现滑膜组织块培养物可组成性产生高水平的LIF。分离的滑膜细胞可自发产生低水平的LIF，但白细胞介素（IL）-1β可使其分泌增加4倍。抗炎细胞因子IL-4使滑膜组织块产生的LIF减少75%，这与之前观察到的IL-6、IL-1β和肿瘤坏死因子（TNF）-α的作用相同。IL-4具有直接作用，因为它可抑制未受刺激以及受IL-1β或TNF-α刺激的滑膜细胞产生LIF。相反，IL-4可增强IL-6的产生，IL-6与LIF具有共同的生物学活性和受体成分。IL-4的抑制作用呈剂量依赖性，使用抗IL-4受体阻断抗体可逆转这种作用。在骨关节炎患者的滑膜组织块和正常滑膜细胞上也观察到IL-4对LIF产生具有类似的抑制作用。另一种作用于单核细胞的抗炎细胞因子IL-10对滑膜组织块或分离的滑膜细胞产生LIF均无影响。因此，IL-4通过对滑膜细胞的直接作用以及抑制LIF诱导细胞因子的产生的间接作用来抑制滑膜组织产生LIF。
