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Volume 60, Issue 6, Pages 2118-2128 (December 2001)
Interleukin-10 inhibits ischemic and cisplatin-induced acute renal injury Jiangping Deng, Yukimasa Kohda, Hsi Chiao, Yuqin Wang, Xuxhen Hu, Stephen M. Hewitt, Takehiko Miyaji, Paul Mcleroy, Bobby Nibhanupudy, Shujun Li, Robert A. Star, M.D. Kidney International Volume 60, Issue 6, Pages (December 2001) DOI: /j x Copyright © 2001 International Society of Nephrology Terms and Conditions
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Figure 1 Dose dependency of interleukin-10 (IL-10) on renal function following cisplatin administration in (A) BALB/c and (B) C57BL6 mice. Animals were given 20 mg/kg cisplatin IP, and either vehicle or 0.1, 0.5 or 1 μg IL-10 by IV injection at the time of cisplatin administration (3 to 5 BALB/c and 2 C57BL/6 mice per group). Blood was obtained at 48 and 72 hours. Animals were sacrificed at 72 hours. Data are mean ± 1 SE. *P < 0.05 vs. no IL-10 by ANOVA. Kidney International , DOI: ( /j x) Copyright © 2001 International Society of Nephrology Terms and Conditions
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Figure 2 Effect of IL-10 on renal function following cisplatin administration. BALB/c mice received IP cisplatin and vehicle (•) or 1 μg IL-10 by IV injection at the time of cisplatin administration (○). Data are mean ± 1 SE. N = 8 to 10 animals per group. *P < 0.05. Kidney International , DOI: ( /j x) Copyright © 2001 International Society of Nephrology Terms and Conditions
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Figure 3 Typical histology and leukocyte accumulation following cisplatin administration. Mice were studied 72 hours after cisplatin (A, B) or 24 hours after 40 minutes of ischemia (C, D). Mice were treated with vehicle (A, C) or IL-10 (B, D). Sections stained with H&E. Kidney International , DOI: ( /j x) Copyright © 2001 International Society of Nephrology Terms and Conditions
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Figure 4 Effects of IL-10 on semiquantitative histology and quantitative leukocyte accumulation, TUNEL, and PCNA staining in BALB/c mice following cisplatin administration. A description of the methodology is in the Methods section. Symbols are: (▪) vehicle; () IL-10. Data are mean ± 1 SE. Number of animals are 4 to 8 cisplatin, and 3 cisplatin + IL-10. *P < 0.05 vs. vehicle. Kidney International , DOI: ( /j x) Copyright © 2001 International Society of Nephrology Terms and Conditions
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Figure 5 Effect of delayed IL-10 on renal function following cisplatin administration. Animals received 1 μg IL-10 IV one hour after cisplatin. Data are mean ± 1 SE. Data from BALB/c mice are displayed as circles; C57BL/6 mice are shown as squares; open symbols are vehicle and closed symbols are IL-10. *P < 0.05. Kidney International , DOI: ( /j x) Copyright © 2001 International Society of Nephrology Terms and Conditions
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Figure 6 Effect of IL-10 on renal function following ischemic injury. BALB/c mice were subjected to 40 minutes of ischemia, received vehicle or 0.5 μg IL-10 IP after clamp release, and sacrificed after 24 hours. Number of animals are 3 sham, 5 ischemia, and 6 ischemia + IL-10. *P < 0.05. Kidney International , DOI: ( /j x) Copyright © 2001 International Society of Nephrology Terms and Conditions
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Figure 7 Effects of IL-10 on semiquantitative histology and quantitative leukocyte counts in BALB/c mice subjected to 40 minutes of ischemia. A description of the methodology is in the Methods section. Data are mean ± 1 SE. Number of animals are 3 sham, 5 ischemia, and 6 ischemia + IL-10. Symbols are: (▪) vehicle; () IL-10; *P < 0.05 vs. vehicle. Kidney International , DOI: ( /j x) Copyright © 2001 International Society of Nephrology Terms and Conditions
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Figure 8 Effect of α-melanocyte stimulating hormone (α-MSH), interleukin-10 (IL-10), or both agents on recovery from transplantation of a kidney subjected to 40 minutes of warm ischemia. Six to 7 animals per group; details are in the text. Symbols are: () vehicle; (○) α-MSH; (□) IL-10; (•) α-MSH + IL- 10. P < 0.05 vs. vehicle by ANOVA for α-MSH on days 2, 3, and 5; IL-10 on days 2, 5, 7; MSH and IL-10 on days 2, 3, and 5. Kidney International , DOI: ( /j x) Copyright © 2001 International Society of Nephrology Terms and Conditions
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Figure 9 Effect of IL-10 on mRNA abundance of TNF-α, intracellular adhesion molecule-1 (ICAM-1), and inducible nitric oxide synthase (NOS-II) following cisplatin administration or ischemia/reperfusion. Top: Animals were administered 20 μg/kg cisplatin IV, given vehicle or 1 μg IL-10 IV, and then sacrificed at 4 hours. The RNA was extracted, and RT/PCR performed as described in the Methods section. Bottom: Animals were subjected to 40 minutes of ischemia, given vehicle or 1 μg IL-10 IV, and then sacrificed at 30 minutes to 4 hours. Kidney International , DOI: ( /j x) Copyright © 2001 International Society of Nephrology Terms and Conditions
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Figure 10 Effect of IL-10 and α-MSH on nitrite production from mouse cortical tubule cells or RAW cells. MCT cells were stimulated with IFN-γ. RAW cells were simulated with LPS. All assays were performed using 3 to 4 replicates, and repeated in at least 4 independent experiments. *P < 0.05 vs. control. The control and α-MSH data were published previously15. Symbols are: (□) control; (▪) IL-10; () α-MSH. Kidney International , DOI: ( /j x) Copyright © 2001 International Society of Nephrology Terms and Conditions
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