Enhanced generation of interleukins 1 beta and 6 may contribute to the cachexia of chronic disease
Enhanced generation of interleukins 1 beta and 6 may contribute to the cachexia of chronic disease
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DOI：
10.1093/ajcn/65.3.876
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发表时间：
1997-03-01
影响因子：
7.1
通讯作者：
Palmblad, J
中科院分区：
文献类型：
--
作者：
Cederholm, T;Wretlind, B;Palmblad, J
疾病的恶病质可由促炎性细胞因子例如白细胞介素（IL）1 β、肿瘤坏死因子α（TNF-α）和IL-6促进。这些，以及一些炎症细胞因子，如IL-1受体拮抗剂（IL-1 ra），IL-10和转化生长因子β 1（TGF-β 1），分析血清（IL-6，IL-1 ra，IL-10，TGF-β 1）和刺激的血液单核细胞（IL-1 β，TNF α，IL-6）从老年患者蛋白质能量营养不良（PEM）。21例未感染的营养不良患者，年龄75 ± 1岁，体重指数（BMI;单位kg/m2）为17.2 ± 0.5，伴有各种非癌症疾病; 22例健康匹配的对照组，年龄72 ± 1岁，BMI为25.4 ± 0.7（与患者相比有显著差异，P < 0.001）。15例患者及其相应的对照组于3个月后复查。用脂多糖（LPS）刺激分离的单核细胞，并测定IL-1 β、TNF-α和IL-6的浓度。分析IL-6、IL-1 ra、IL-10、TGF-β 1和急性期反应物的血清浓度。营养不良受试者的血清类粘蛋白和IL-6浓度高于对照受试者（分别为1.14 +/- 0.1和0.8 +/- 0.3 g/L，P < 0.001; 5 ng/L和检测不到的浓度，P < 0.01）。当单核细胞用0.1 μ g LPS/L刺激时，发现PEM患者的单核细胞产生的IL-1 β（2.7倍; P <0.05）和IL-6（3.7倍; P < 0.05）高于对照受试者。单核细胞TNF生成和IL-10、IL-1 ra和TGF-β 1的血清浓度没有差异。在随访时获得了类似的结果。IL-1 ra与迟发性皮肤超敏反应呈负相关（r =-0.34，P < 0.05）。我们的结论是，促炎细胞因子，如IL-6和IL-1 β在营养不良的患者中的增强产生可能有助于PEM经常遇到的慢性非恶性疾病。
The cachexia of disease may be promoted by proinflammatory cytokines, eg, interleukin (IL) 1 beta, tumor necrosis factor alpha (TNF-alpha), and IL-6. These, as well as some antiinflammatory cytokines, eg, IL-1 receptor antagonist (IL-1ra), IL-10, and transforming growth factor beta 1 (TGF-beta 1), were analyzed in serum (IL-6, IL-1ra, IL-10, TGF-beta 1) and stimulated blood monocytes (IL-1 beta, TNF alpha, IL-6) obtained from elderly patients with protein-energy malnutrition (PEM). Twenty-one uninfected malnourished patients aged 75 +/- 1 y , with a body mass index (BMI; in kg/m(2)) of 17.2 +/- 0.5 and various noncancer disorders, and 22 healthy matched control subjects aged 72 +/- 1 y, with a BMI of 25.4 +/- 0.7 (significantly different from patients, P < 0.001), were included. Fifteen patients and their corresponding control subjects were reexamined 3 mo later. Isolated monocytes were stimulated with lipopolysaccharide (LPS) and concentrations of IL-1 beta, TNF-alpha, and IL-6 were determined. Serum concentrations of IL-6, IL-1ra, IL-10, TGF-beta 1, and acute-phase reactants were analyzed. Serum concentrations of orosomucoid and IL-6 were higher in the malnourished subjects than in the control subjects (1.14 +/- 0.1 compared with 0.8 +/- 0.3 g/L, P < 0.001; and 5 ng/L compared with undetectable concentrations, P < 0.01, respectively). Higher generation of IL-1 beta (2.7-fold; P < 0.05) and IL-6 (3.7-fold; P < 0.05) was found in monocytes from patients with PEM relative to the control subjects when monocytes were stimulated with 0.1 mu g LPS/L. Monocyte TNF generation and serum concentrations of IL-10, IL-1ra, and TGF-beta 1 did not differ. Similar results were obtained at follow-up. IL-1ra was negatively correlated with delayed cutaneous hypersensitivity (r = -0.34, P < 0.05). We conclude that enhanced generation of proinflammatory cytokines such as IL-6 and IL-1 beta in malnourished patients may contribute to the PEM often encountered in chronic nonmalignant disorders.