Frankenberger M, Pechumer H, Ziegler-Heitbrock H W
Institute for Immunology, University of Munich, Germany.
J Inflamm. 1995;45(1):56-63.
Lipopolysaccharide (LPS) stimulation of the human monocytic cell line Mono Mac 6 leads to rapid expression of both the pro-inflammatory cytokine tumor necrosis factor (TNF) and the anti-inflammatory cytokine interleukin-10 (IL-10). Preculture of these cells with a low dose of LPS for 2 days rendered the cells tolerant to subsequent stimulation, in that TNF gene expression is only minimal, both at the mRNA and at the protein level. IL-10 shows a reciprocal pattern, however, as expression of this gene is upregulated in precultured cells, and it will further increase upon subsequent stimulation. Although TNF has been shown to induce IL-10, and IL-10 was found to downregulate TNF, this reciprocal regulation does not explain the pattern observed in LPS tolerance in Mono Mac 6, since neutralizing antibodies against TNF and IL-10 could not prevent upregulation of IL-10 and downregulation of TNF, respectively. Treatment of Mono Mac 6 cells during LPS preculture with interferon-gamma (IFN-gamma) could, however, reverse tolerance: LPS/IFN-gamma precultured cells produced high levels of TNF transcripts upon subsequent stimulation, while the response of the IL-10 gene was attenuated. The data show that LPS tolerance does not involve a passive downregulation of all types of monocyte functions, but it is an orchestrated response with downregulation of pro- and upregulation of anti-inflammatory cytokines.
脂多糖（LPS）刺激人单核细胞系Mono Mac 6会导致促炎细胞因子肿瘤坏死因子（TNF）和抗炎细胞因子白细胞介素-10（IL-10）迅速表达。用低剂量LPS对这些细胞进行预培养2天，会使细胞对后续刺激产生耐受，即TNF基因在mRNA和蛋白质水平的表达都仅为最低限度。然而，IL-10呈现出相反的模式，因为该基因在预培养细胞中的表达上调，并且在后续刺激时会进一步增加。尽管已证明TNF可诱导IL-10，且发现IL-10可下调TNF，但这种相互调节并不能解释在Mono Mac 6细胞LPS耐受中观察到的模式，因为针对TNF和IL-10的中和抗体分别无法阻止IL-10的上调和TNF的下调。然而，在LPS预培养期间用干扰素-γ（IFN-γ）处理Mono Mac 6细胞可逆转耐受：LPS/IFN-γ预培养的细胞在后续刺激时产生高水平的TNF转录本，而IL-10基因的反应则减弱。数据表明，LPS耐受并不涉及所有类型单核细胞功能的被动下调，而是一种有组织的反应，包括促炎细胞因子的下调和抗炎细胞因子的上调。
