Ellaban Ekram, Bolgos Gerry, Remick Daniel
Department of Pathology, University of Michigan Medical School, Ann Arbor, MI 48109-0602, USA.
Cell Immunol. 2004 Sep-Oct;231(1-2):103-11. doi: 10.1016/j.cellimm.2004.12.010. Epub 2005 Feb 26.
Polymicrobial sepsis induces suppression of macrophage function as determined by a reduction of pro-inflammatory cytokine production upon re-exposure to lipopolysaccharide (LPS) in vitro. We examined whether macrophages were refractory to only LPS challenge or if they were immunoparalyzed and unable to respond to other stimuli such as lipoteichoic acid (LTA) or zymosan (ZYM). This study evaluated the capacity of peritoneal macrophages to produce pro-inflammatory and anti-inflammatory cytokines as well as chemokines following mild or severe sepsis induced by cecal ligation and puncture (CLP). Peritoneal macrophages were isolated 29 h after CLP and challenged with different stimuli. LPS was a more potent stimulus for cytokine induction than LTA or ZYM in both mild and severe sepsis. In mild sepsis, the macrophage cytokine response to LPS was selective and less refractory than in severe sepsis. While production of IL-6 and KC was reduced, secretion of TNF-alpha and MIP-1alpha was enhanced in those cells isolated from mice with mild sepsis. Production of IL-10 and the IL-1 receptor antagonist , MIP-2, and MCP-1 in response to LPS stimulation was equivalent to the amount produced by naive macrophages. Our results indicate that macrophages are not immunoparalyzed during sepsis and may still be induced to secrete some inflammatory mediators.
多种微生物引起的败血症会导致巨噬细胞功能受到抑制，这可通过体外再次接触脂多糖（LPS）后促炎细胞因子产生减少来确定。我们研究了巨噬细胞是否仅对LPS刺激具有抗性，或者它们是否处于免疫麻痹状态而无法对其他刺激（如脂磷壁酸（LTA）或酵母聚糖（ZYM））作出反应。本研究评估了在盲肠结扎和穿刺（CLP）诱导的轻度或重度败血症后，腹膜巨噬细胞产生促炎和抗炎细胞因子以及趋化因子的能力。CLP后29小时分离腹膜巨噬细胞，并用不同刺激物进行刺激。在轻度和重度败血症中，LPS都是比LTA或ZYM更强的细胞因子诱导刺激物。在轻度败血症中，巨噬细胞对LPS的细胞因子反应具有选择性，且比在重度败血症中更不易产生抗性。虽然从轻度败血症小鼠分离的那些细胞中IL-6和KC的产生减少，但TNF-α和MIP-1α的分泌增加。对LPS刺激产生的IL-10、IL-1受体拮抗剂、MIP-2和MCP-1的量与未感染巨噬细胞产生的量相当。我们的结果表明，败血症期间巨噬细胞并非处于免疫麻痹状态，并且可能仍可被诱导分泌一些炎症介质。
