Tumor Necrosis Factor-α Antagonist Etanercept Decreases Blood Pressure and Protects the Kidney in a Mouse Model of Systemic Lupus Erythematosus

被引：146

作者：

Venegas-Pont, Marcia ^{[1
,2
]}

Manigrasso, Michaele B. ^{[1
,2
]}

Grifoni, Samira C. ^{[1
,2
]}

LaMarca, Babbette B. ^{[1
,2
]}

Maric, Christine ^{[1
,2
]}

Racusen, Lorraine C. ^{[3
]}

Glover, Porter H. ^{[1
,2
]}

Jones, Allison V. ^{[1
,2
]}

Drummond, Heather A. ^{[1
,2
]}

Ryan, Michael J. ^{[1
,2
]}

机构：

[1] Univ Mississippi, Med Ctr, Dept Physiol & Biophys, Jackson, MS 39216 USA

[2] Univ Mississippi, Med Ctr, Ctr Excellence Cardiovasc Renal Res, Jackson, MS 39216 USA

[3] Johns Hopkins Univ Hosp, Dept Pathol, Baltimore, MD 21287 USA

来源：

HYPERTENSION | 2010年 / 56卷 / 04期

基金：

美国国家卫生研究院;

关键词：

systemic lupus erythematosus; hypertension; inflammation; TNF-alpha; oxidative stress; cytokine; TNF-ALPHA; OXIDATIVE STRESS; RENAL-DISEASE; RISK-FACTORS; HYPERTENSION; EXPRESSION; INFLIXIMAB; THERAPY; DEFICIENCY; CYTOKINES;

D O I：

10.1161/HYPERTENSIONAHA.110.157685

中图分类号：

R6 [外科学];

学科分类号：

100210 [外科学];

摘要：

Chronic inflammation has been implicated in the pathology of hypertension; however, the role for specific cytokines remains unclear. We tested whether tumor necrosis factor-alpha blockade with etanercept (Etan) reduces mean arterial pressure in a female mouse model of systemic lupus erythematosus (SLE). SLE is a chronic inflammatory disorder with prevalent hypertension. Thirty-week-old SLE (NZBWF1) and control mice (NZW/LacJ) received Etan (0.8 mg/kg SC weekly) for 4 weeks or vehicle. Mean arterial pressure (in millimeters of mercury) was increased in SLE mice (150 +/- 5 versus 113 +/- 5 in controls; P < 0.05) and was lower in Etan-treated SLE mice (132 +/- 3) but not controls (117 +/- 5). Albuminuria (in micrograms per milligram of creatinine) was elevated in SLE mice (28 742 +/- 9032 versus 1075 +/- 883; P < 0.05) and was lower in Etan-treated SLE mice (8154 +/- 3899) but not control animals (783 +/- 226). Glomerulosclerosis (in percentage of glomeruli) was evident in SLE mice (2.5 +/- 1.6 versus 0.0 +/- 0.0 in controls; P < 0.05) and was ameliorated in Etan-treated SLE mice (0.1 +/- 0.1). Renal cortex CD68(+) cell staining (in percentage of area) was elevated in SLE mice (4.75 +/- 0.80 versus 0.79 +/- 0.12 in controls; P < 0.05) and was lower in Etan-treated SLE mice (2.28 +/- 0.32) but not controls (1.43 +/- 0.25). Renal cortex NADPH oxidase activity (relative light units per milligram of protein) was higher in SLE mice compared with controls (10 718 +/- 1276 versus 7584 +/- 229; P +/- 0.05) and lowered in Etan-treated SLE mice (6645 +/- 490). Renal cortex nuclear factor kappa B (phosphorylated and nonphosphorylated) was increased in SLE mice compared with controls and lower in Etan-treated SLE mice. These data suggest that TNF-alpha mechanistically contributes to the development of hypertension in a chronic inflammatory disease through increased renal nuclear factor kappa B, oxidative stress, and inflammation. (Hypertension. 2010;56:643-649.)

引用

页码：643 / 649

页数：7

共 46 条

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Adverse events and efficacy of TNF-α blockade with infliximab in patients with systemic lupus erythematosus: long-term follow-up of 13 patients [J].