Role of IL-1 in renal ischemic reperfusion injury.

Abstract

Interleukin-1 (IL-1) is a central component of many acute inflammatory processes. Blocking IL-1 receptor (IL-1R) with IL-1R antagonist (IL-1Ra) has attenuated ischemic reperfusion injury in brain, heart, and liver models. However, the role of IL-1 in renal ischemic reperfusion injury (IRI) is not known. Therefore, the role of IL-1 in renal IRI was evaluated using the complementary approaches of IL-1R blockade in wild-type mice in addition to the study of renal IRI in IL-1R knockout (KO) mice. Ischemia was induced by bilateral renal pedicle clamping for 30 min. IL-1Ra was administered at 10 mg/kg every 4 h, high doses that have been protective in previous organ injury models in mice. IL-1R KO animals, previously characterized as insensitive to IL-1, had the absence of IL-1R1 confirmed by DNA blots. IL-1Ra, IL-1R KO, and control groups had similar elevations of blood urea nitrogen (114 +/- 13, 133 +/- 11, and 120 +/- 11 mg/dl) and serum creatinine (1.7 +/- 0.3, 2.1 +/- 0.2, and 1.6 +/- 0.3 mg/dl) 24 h after ischemia. Furthermore, acute tubular necrosis scores were also similar in IL-1Ra-treated mice (3.0 +/- 0.3), IL-1R KO mice (2.7 +/- 0.3), and control mice (3.1 +/- 0.2). However, both IL-1Ra and IL-1R KO groups, compared with control animals, developed significantly less infiltration of polymorphonuclear leukocytes per 10 high-power fields in postischemic renal tissue (1111 +/- 228 and 967 +/- 198 versus 1820 +/- 190, P < 0.05). In contrast to the comparable renal functions at 24 h, recovery of renal function was significantly accelerated in the IL-1R KO group compared with control at both 48 (P < 0.05) and 72 (P < 0.05) h. Recovery in the IL-1Ra group was similar to that in the control animals. These data demonstrate that IL-1 is unlikely to be beneficial in the recovery of renal function after ischemia and may play a deleterious role.

Molecular RNA Correlates of the SOFA Score in Patients with Sepsis

“…Among these, PARP1 appeared to have protective renal effects in knock-out mouse models of ischemic injury [25]. In contrast to PPAR1, IL1R1 (interleukin receptor 1) resulted in lower creatinine blood concentrations in models of ischemic injury [26].…”

Divergent Actions of Renal Tubular and Endothelial Type 1 IL-1 Receptor Signaling in Toxin-Induced AKI

“…For example, IL-1R1 blockade failed to attenuate murine ischemic AKI but mitigated renal tubular damage and apoptosis in a rat model of renal IRI. 6,61 While the reasons for some discrepant effects of IL-1R1 receptor antagonism versus deficiency are unclear, our findings in this study offer one explanation that IL-1 signaling may exert cell lineage–specific opposing roles in acute renal damage.…”

Maslinic Acid Attenuates Ischemia/Reperfusion-Induced Acute Kidney Injury by Suppressing Inflammation and Apoptosis Through Inhibiting NF-κB and MAPK Signaling Pathway

“…Kelly et al reported that the gene-deficient adhesion molecule ICAM-1 could protect against renal injury in an animal model of renal ischemia ( Kelly et al, 1996 ). In addition, renal tubular epithelial cells can also contribute to the inflammatory response to renal IR injury by producing various pro-inflammatory cytokines (e.g., TNF-α, IL-1β) and chemokines (e.g., MCP-1) ( Haq et al, 1998 ; Sung et al, 2002 ; Spurgeon et al, 2005 ). In the present study, pro-inflammatory cytokines and cell adhesion molecules were decreased in vitro and in vivo following MA administration, indicating that MA may ameliorate IRI by inhibiting the inflammatory response.…”