Plasma interferon-γ and interleukin-10 concentrations in systemic meningococcal disease compared with severe systemic Gram-positive septic shock
Plasma interferon-γ and interleukin-10 concentrations in systemic meningococcal disease compared with severe systemic Gram-positive septic shock
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DOI：
10.1097/01.ccm.0000104950.52577.97
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发表时间：
2004-02-01
影响因子：
8.8
通讯作者：
Brandtzaeg, P
中科院分区：
文献类型：
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作者：
Bjerre, A;Brusletto, B;Brandtzaeg, P
目的：分析全体性脑膜炎球菌病及肺炎链球菌、金黄色葡萄球菌所致严重革兰氏阳性脓毒性休克患者血浆干扰素- γ和白细胞介素-10的含量。研究重组白细胞介素-10或重组干扰素- γ对热杀脑膜炎奈瑟菌、肺炎链球菌和金黄色葡萄球菌全血模型体外细胞因子（干扰素- γ和白细胞介素-10）反应的影响。设计：实验研究。设置:实验室。对象：采集系统性脑膜炎球菌病患者（66例）和由肺炎链球菌（4例）或金黄色葡萄球菌（3例）引起的严重革兰氏阳性感染性休克患者的血浆样本。干预措施：用热杀死的脑膜炎奈瑟菌、肺炎奈瑟菌和金黄色葡萄球菌（1 × 10(6)菌落形成单位/mL）增强全血，并在0、5、12和24小时分析血浆中白细胞介素-10或干扰素- γ。在细菌前添加重组白细胞介素-10或重组干扰素- γ，并在24 h后分别分析对干扰素- γ和白细胞介素-10分泌的影响。测量和主要结果。脑膜炎球菌感染性休克患者（n = 24）干扰素- γ的中位浓度为15 pg/mL，白介素-10的中位浓度为10269 pg/mL，而严重革兰氏阳性休克患者的中位浓度为3400 pg/mL，白介素-10的中位浓度为465 pg/mL （p = 0.001）。干扰素浓度升高与病死率相关（p = 0.011）。在全血模型中，我们证明了1 x 10(6)个菌落形成单位/mL的脑膜炎奈瑟菌比肺炎奈瑟菌诱导更多的白细胞介素-10而较少的干扰素- γ。金黄色葡萄球菌诱导的这两种细胞因子的分泌都很少。重组白细胞介素-10在全血模型中有效下调干扰素- γ的分泌，反之亦然。结论：我们推测暴发性脑膜炎球菌败血症中高浓度的白细胞介素-10可能导致低浓度的干扰素- γ。此外，干扰素γ似乎在脑膜炎球菌感染性休克的病理生理中起次要作用。
Objective: To analyze plasma interferon-gamma and interleukin-10 concentrations in patients with systemic meningococcal disease and patients with severe Gram-positive septic shock caused by Streptococcus pneumoniae or Staphylococcus aureus. To study the in vitro cytokine (interferon-gamma and interleukin-10) responses in a whole blood model boosted with heat-killed Neisseria meningitidis, S. pneumoniae, and S. aureus before and after treatment with recombinant interleukin-10 or recombinant interferon-gamma.Design: Experimental study.Setting: Laboratory.Subjects: Plasma samples were collected from patients with systemic meningococcal disease (n = 66) and patients with severe Gram-positive septic shock caused by S. pneumoniae (n = 4) or S. aureus (n = 3).Interventions: Whole blood was boosted with heat-killed N. meningitidis, S. pneumoniae, and S. aureus (1 x 10(6) colony forming units/mL), and plasmas were analyzed for interleukin-10 or interferon-gamma at 0, 5, 12, and 24 hrs. Furthermore, recombinant interleukin-10 or recombinant interferon-gamma was added before bacteria, and the effect on the secretion of interferon-gamma and interleukin-10, respectively, was analyzed after 24 hrs.Measurements and Main Results. The median concentration of interferon-gamma was 15 pg/mL and of interleukin-10 was 10,269 pg/mL in patients with meningococcal septic shock (n = 24) compared with median interferon-gamma concentration of 3400 pg/mL and interleukin-10 concentration of 465 pg/mL in patients with severe Gram-positive shock (p = .001). Increased interferon-gamma concentrations were associated with case fatality (p = .011). In a whole blood model we demonstrated that 1 x 10(6) colony forming units/mL of N. meningitidis induced more interleukin-10 but less interferon-gamma than S. pneumoniae. S. aureus induced minimal secretion of both cytokines. Recombinant interleukin-10 efficiently down-regulated the secretion of interferon-gamma, and vice versa, as shown in a whole blood model.Conclusion: We speculate whether high concentrations of interleukin-10 contribute to the low concentrations of interferon-gamma in fulminant meningococcal septicemia. In addition, it appears as if interferon-gamma plays a minor role in the pathophysiology of meningococcal septic shock.