The TNF-α antagonist etanercept decreases blood pressure and protects the kidney in a mouse model of systemic lupus erythematosus

• Published in: Hypertension (Dallas, Tex. 1979) Vol. 56; no. 4; pp. 643 - 649
• Main Authors: Venegas-Pont, Marcia, Manigrasso, Michaele B., Grifoni, Samira C., LaMarca, Babbette B., Maric, Christine, Racusen, Lorraine C., Glover, Porter H., Jones, Allison V., Drummond, Heather A., Ryan, Michael J.
• Format: Journal Article
• Language: English
• Published: 09.08.2010
• ISSN: 0194-911X; 1524-4563
• DOI: 10.1161/HYPERTENSIONAHA.110.157685

Chronic inflammation has been implicated in the pathology of hypertension; however, the role for specific cytokines remains unclear. We tested whether TNF-α blockade with etanercept (Etan) reduces mean arterial pressure (MAP) 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 (0.8mg/kg SC weekly) for 4 weeks or vehicle. MAP (mmHg) was increased in SLE mice (150±5 vs. 113±5 in controls, p<0.05) and was lower in Etan treated SLE mice (132±3) but not controls (117±5). Albuminuria (µg/mg creatinine) was elevated in SLE mice (28742±9032 vs. 1075±883 p<0.05) and was lower in Etan treated SLE mice (8154±3899) but not control animals (783±226). Glomerulosclerosis (% of glomeruli) was evident in SLE mice (2.5±1.6 vs. 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 (% area) was elevated in SLE mice (4.75±0.80 vs. 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 (RLU/mg of protein) was higher in SLE mice compared to controls (10718±1276 vs. 7584±229, p<0.05) and lowered in Etan treated SLE mice (6645±490). Renal cortex NFκB (phosphorylated and non-phosphorylated) was increased in SLE mice compared to controls and lower in Etan treated SLE mice. These data suggest that TNF-α mechanistically contributes to the development of hypertension in a chronic inflammatory disease through increased renal NFκB, oxidative stress and inflammation.