Abstract 007: Interleukin-6 Inhibition Attenuates Hypertension and Associated Renal Damage in Dahl Salt-sensitive (SS) Rats

Abstract

Data from our lab indicates that infiltration of T lymphocytes into the kidney amplifies salt-sensitive hypertension and renal damage in SS rats. Interestingly, interleukin 6 (IL-6) mRNA is >50-fold higher in T cells isolated from the kidney in comparison to circulating T cells. Experiments were performed to assess the role of IL-6 in Dahl SS rats (n=13-14/group) fed low salt chow until 9 weeks of age and subsequently treated with goat anti-rat IL-6 neutralizing antibody (anti-rIL-6; 4 μg /day, IP; R&D Systems, Minneapolis, MN) or normal goat IgG control (4 μg /day, IP) during an 11 day period of high salt intake. The MAP and urine albumin excretion rates (Ualb) were not different between the groups when fed low NaCl chow (MAP=121±1.6 mmHg versus 122±1.8 mmHg and Ualb=15±2mg/day versus 12±1.7 mg/day in the vehicle-treated versus anti-rIL-6-treated rats). Following 11 days of drug-treatment, the rats receiving anti-rIL-6 demonstrated a significant 47% reduction in IL-6 in the renal medulla compared to vehicle-treated SS. Moreover, the increase in MAP following 11 days of high NaCl intake was significantly attenuated in SS administered anti-rIL-6 (MAP=138±3 mmHg) compared with the control group (MAP=149±3 mmHg). The renal damage was also attenuated in SS administered anti-rIL-6; Ualb was significantly reduced in the treated (109±10 mg/day) compared to the control group (151±16 mg/day) and glomerular and tubular damage were also attenuated. To investigate potential mechanisms of action, a flow cytometric analysis of infiltrating immune cells in the kidney (n=4-5/group) was performed. The total number of leukocytes (CD45+) was significantly lower in the treatment vs the control group (4.8±0.5x106 vs 6.8±0.5x106 cells/kidney). Infiltrating monocytes and macrophages (CD11b/c+) were also significantly lower in the treatment vs the control group (3.7±0.3x106 vs 5.4±0.3x106 cells/kidney). The total number of infiltrating T and B lymphocytes was not different among the groups. The present studies indicate that IL-6 production may participate in the development of SS hypertension and end-organ damage by mediating the recruitment and infiltration of macrophages into the kidney.