Cebon J, Layton J E, Maher D, Morstyn G
Ludwig Institute for Cancer Research, Melbourne Tumour Biology Branch, Parkville, Victoria, Australia.
Br J Haematol. 1994 Feb;86(2):265-74. doi: 10.1111/j.1365-2141.1994.tb04725.x.
Haemopoietic growth factors (HGFs) are being administered to patients with neutropenic fever; however, little is known about the endogenous HGF response in these patients. Specific assays were used to study four HGFs, granulocyte (G-) CSF, granulocyte-macrophage (GM-) CSF, macrophage (M-) CSF and interleukin (IL-) 6 levels in the blood of patients with neutropenic fever (46 episodes). For comparison, levels were also measured in three control populations: normals (20), afebrile neutropenic (14), and bacteraemic but not neutropenic patients (20). In febrile patients, levels of G-CSF (median, range) (0.46, < 0.10-142 ng/ml). IL-6 (0.054, 0.005-24.3 ng/ml) and M-CSF (18.5, 9.9-79.1 ng/ml) were elevated compared with afebrile subjects (< 0.10, < 0.10-1.62 ng/ml). (0.008, 0.002-0.024 ng/ml) and (6.45, < 5.0-31.3 ng/ml) respectively. GM-CSF was not elevated (< 0.02, < 0.02-8.0 ng/ml) compared with afebrile subjects (0.021, < 0.02-0.20 ng/ml). Variables significantly associated (P < 0.05) with elevated cytokine levels were determined by multiple regression analyses. Factors associated with G-CSF elevation were fever, neutropenia, pathogen type and raised bilirubin and creatinine. In contrast, neutropenia was not associated with IL-6 elevation although there was an association between IL-6 elevation and fever, Gram-negative and fungal infections and raised creatinine and bilirubin. M-CSF elevation was associated with fever, renal impairment and known pathogen. Elevated G-CSF and IL-6 levels normalized rapidly (hours-days) with the resolution of infection, whereas M-CSF concentrations remained elevated for up to 10 d. Cytokine levels remained elevated in septic neutropenic patients who did not recover. In summary, G-CSF, IL-6 and M-CSF levels were significantly elevated in sepsis. In contrast, GM-CSF levels were not elevated. These studies should assist the development of therapeutic strategies using HGFs in the treatment of sepsis.
造血生长因子（HGFs）正被用于治疗中性粒细胞减少伴发热的患者；然而，对于这些患者内源性HGF的反应了解甚少。采用特定检测方法研究了46例中性粒细胞减少伴发热患者血液中的四种HGF，即粒细胞集落刺激因子（G-CSF）、粒细胞-巨噬细胞集落刺激因子（GM-CSF）、巨噬细胞集落刺激因子（M-CSF）和白细胞介素（IL-6）水平。为作比较，还检测了三个对照人群的水平：正常人（20例）、无发热的中性粒细胞减少患者（14例）以及有菌血症但无中性粒细胞减少的患者（20例）。在发热患者中，G-CSF水平（中位数，范围）（0.46，<0.10 - 142 ng/ml）、IL-6水平（0.054，0.005 - 24.3 ng/ml）和M-CSF水平（18.5，9.9 - 79.1 ng/ml）与无发热受试者相比有所升高（<0.10，<0.10 - 1.62 ng/ml）、（0.008，0.002 - 0.024 ng/ml）和（6.45，<5.0 - 31.3 ng/ml）。与无发热受试者（0.021，<0.02 - 0.20 ng/ml）相比，GM-CSF水平未升高（<0.02，<0.02 - 8.0 ng/ml）。通过多元回归分析确定了与细胞因子水平升高显著相关（P<0.05）的变量。与G-CSF升高相关的因素有发热、中性粒细胞减少、病原体类型以及胆红素和肌酐升高。相比之下，中性粒细胞减少与IL-6升高无关，尽管IL-6升高与发热、革兰氏阴性菌和真菌感染以及肌酐和胆红素升高有关。M-CSF升高与发热、肾功能损害和已知病原体有关。随着感染的消退，升高的G-CSF和IL-6水平迅速（数小时至数天）恢复正常，而M-CSF浓度在长达10天内仍保持升高。未恢复的脓毒症中性粒细胞减少患者的细胞因子水平持续升高。总之，脓毒症时G-CSF、IL-6和M-CSF水平显著升高。相比之下，GM-CSF水平未升高。这些研究应有助于开发在脓毒症治疗中使用HGF的治疗策略。
