胰岛素样生长因子1对正常和脓毒症状态下中性粒细胞及单核细胞功能的影响。

Effects of insulin-like growth factor 1 on neutrophil and monocyte functions in normal and septic states.

作者信息

Balteskard L, Unneberg K, Halvorsen D, Hansen J B, Revhaug A

机构信息

Department of Surgery, Tromsø University Hospital, Norway.

出版信息

JPEN J Parenter Enteral Nutr. 1998 May-Jun;22(3):127-35. doi: 10.1177/0148607198022003127.

DOI:10.1177/0148607198022003127

PMID:9586789

Abstract

BACKGROUND

Insulin-like growth factor 1 (IGF-1) mediates anabolic actions in catabolic states and also influences the immune system. Endogenous IGF-1 production is suppressed in sepsis; replacement therapy is therefore a natural approach to obtain the protein anabolic and potentially immune-stimulating effects of IGF-1.

METHODS

Twenty-two piglets were randomized to three groups: an IGF-1 group (n = 8) receiving a continuous infusion of 1.3 mg/h of IGF-1, a nontreated septic control group (n = 8), and a nonseptic control group (n = 6) receiving saline. Phagocytosis and respiratory burst in porcine neutrophils were evaluated by flow cytometry (FCM); tumor necrosis factor (TNF) levels were measured in serum during the septic period. In addition, human neutrophils and monocytes were primed in vitro with IGF-1 and subsequently were stimulated with phorbol myristate acetate (PMA) or Escherichia coli; phagocytosis and respiratory burst were evaluated by FCM.

RESULTS

Under nonseptic conditions, pretreatment with IGF-1 suppressed the ability of neutrophils to ingest bacteria (ie, the level of phagocytosis) 43.4% +/- 2.7% (IGF-1-treated) vs 55.8% +/- 3.4% (nontreated septic controls) and 57.3% +/- 3.34% (nonseptic controls) (p = .01). When challenged by live E. coli infusion, phagocytosis increased in the IGF-1 group to the levels of the nontreated group. The respiratory burst showed a convincing priming effect of IGF-1. After 4 hours of sepsis, the mean fluorescence intensity was 63.1 +/- 6.9 in the IGF-1 group and 40.7 +/- 3.0 in nontreated septic controls. The serum levels of TNF-alpha in the nontreated septic control group were twice those in the IGF-1-treated group, ie, 65.7 +/- 13.1 pg/mL in the nontreated septic controls and 31.5 +/- 7.5 pg/mL in the IGF-1 group (p = .03). In vitro priming of human neutrophils and monocytes with IGF-1 and subsequent stimulation with PMA or E. coli demonstrated that IGF-1 enhanced both phagocytosis and respiratory burst.

CONCLUSIONS

IGF-1 serves as a priming agent for biologic functions of leukocytes.

摘要

背景

胰岛素样生长因子1（IGF-1）在分解代谢状态下介导合成代谢作用，并且还影响免疫系统。脓毒症时内源性IGF-1的产生受到抑制；因此，替代疗法是获得IGF-1的蛋白质合成代谢及潜在免疫刺激作用的自然方法。

方法

22头仔猪被随机分为三组：IGF-1组（n = 8）持续输注1.3 mg/h的IGF-1，未治疗的脓毒症对照组（n = 8），以及接受生理盐水的非脓毒症对照组（n = 6）。通过流式细胞术（FCM）评估猪中性粒细胞的吞噬作用和呼吸爆发；在脓毒症期间测定血清中的肿瘤坏死因子（TNF）水平。此外，人中性粒细胞和单核细胞在体外先用IGF-1进行预处理，随后用佛波酯（PMA）或大肠杆菌进行刺激；通过FCM评估吞噬作用和呼吸爆发。

结果

在非脓毒症条件下，用IGF-1预处理会抑制中性粒细胞摄取细菌的能力（即吞噬水平），经IGF-1处理的为43.4%±2.7%，未治疗的脓毒症对照组为55.8%±3.4%，非脓毒症对照组为57.3%±3.34%（p = 0.01）。当通过输注活大肠杆菌进行刺激时，IGF-1组的吞噬作用增加到未治疗组的水平。呼吸爆发显示出IGF-1具有令人信服的启动作用。脓毒症4小时后，IGF-1组的平均荧光强度为63.1±6.9，未治疗的脓毒症对照组为40.7±3.0。未治疗的脓毒症对照组的血清TNF-α水平是IGF-1治疗组的两倍，即未治疗的脓毒症对照组为65.7±13.1 pg/mL，IGF-1组为31.5±7.5 pg/mL（p = 0.03）。人中性粒细胞和单核细胞在体外先用IGF-1进行预处理，随后用PMA或大肠杆菌进行刺激，结果表明IGF-1增强了吞噬作用和呼吸爆发。