Abstract 43: Renal Hemodynamic and Excretory Responses to Systemic Administration of Interleukin-10 in Anesthetized Mice

Abstract

Recent studies have demonstrated that the anti-inflammatory cytokine, interleukin-10 (IL-10) is normally present in plasma and its protein is constitutively expressed in the renal tissue. However, the possible role of IL-10 in the regulation of renal hemodynamics and excretory function is not yet clearly defined. In the present study, we have examined the systemic and renal responses to intravenous administration of incremental doses of recombinant mouse IL-10 (0.015, 0.075 and 0.15 ng/min/g ; 45 min in each dose) in anesthetized mice (n=5). To determine the specificity of IL-10 actions, the responses to the middle dose were also assessed in the presence of its receptor antagonist, (mouse IL-10 Rα antibody; 1.5 ng/min/g; R&D system) in a separate group of mice (n=6). Standard clearance techniques were used to assess renal responses to infusions of IL-10 and its receptor antagonist. Renal blood flow (RBF) was determined by PAH clearances and glomerular filtration rate (GFR) was determined by inulin clearance. Infusion of IL-10 doses resulted in significant decreases in systemic mean arterial pressure (MAP; 98±1.9 to 89±3.9, 88±2.6 and 84±3.3 mmHg) and renal vascular resistance (RVR, 13.5±1.1 to 9.1±0.6, 7.1±0.5 and 7.1±0.5 mmHg/mL/min/g), increases in RBF (7.4±0.5 to 9.7±0.6, 10.6±0.5 and 9.8±0.6 mL/min/g) and GFR (1.06±0.05 to 1.45±0.13, 1.51±0.13 and 1.53±0.28 mL/min/g) without significant changes in urine flow (6.6±0.5 to 5.3±0.5, 5.5±1.1 and 5.3±1.1 μL/min/g ) or sodium excretion (0.58±0.08 to 0.52±0.18, 0.57±0.19 and 0.69±0.26 μmol/min/g). Administration of IL-10 receptor antagonist alone did not cause significant changes in MAP (90±3.7 to 89±5.3 mmHg), RVR (11.5±1.9 to 11.6±3.0 mmHg/mL/min/g), RBF (8.8±1.3 to 10.4±2.5 mL/min/g), GFR (1.06±0.08 to 1.20±0.19 mL/min/g) or other renal parameters. Infusion of the middle dose of IL-10 in the receptor antagonist pretreated mice failed to cause significant changes in RBF or GFR or other parameters confirming the specificity of its receptor activity in the mediation of observed renal responses to IL-10 infusion. These data suggest that the anti-inflammatory cytokine, IL-10 exerts vasodilator and hyper-filtration effects in the kidney but minimally influences the renal excretory function.