Splenectomy exacerbates lung injury after ischemic acute kidney injury in mice.

Abstract

Patients with acute kidney injury (AKI) have increased serum proinflammatory cytokines and an increased occurrence of respiratory complications. The aim of the present study was to examine the effect of renal and extrarenal cytokine production on AKI-mediated lung injury in mice. C57Bl/6 mice underwent sham surgery, splenectomy, ischemic AKI, or ischemic AKI with splenectomy and kidney, spleen, and liver cytokine mRNA, serum cytokines, and lung injury were examined. The proinflammatory cytokines IL-6, CXCL1, IL-1β, and TNF-α were increased in the kidney, spleen, and liver within 6 h of ischemic AKI. Since splenic proinflammatory cytokines were increased, we hypothesized that splenectomy would protect against AKI-mediated lung injury. On the contrary, splenectomy with AKI resulted in increased serum IL-6 and worse lung injury as judged by increased lung capillary leak, higher lung myeloperoxidase activity, and higher lung CXCL1 vs. AKI alone. Splenectomy itself was not associated with increased serum IL-6 or lung injury vs. sham. To investigate the mechanism of the increased proinflammatory response, splenic production of the anti-inflammatory cytokine IL-10 was determined and was markedly upregulated. To confirm that splenic IL-10 downregulates the proinflammatory response of AKI, IL-10 was administered to splenectomized mice with AKI, which reduced serum IL-6 and improved lung injury. Our data demonstrate that AKI in the absence of a counter anti-inflammatory response by splenic IL-10 production results in an exuberant proinflammatory response and lung injury.

• Authors: Ana Andrés-Hernando, Christopher Altmann, Nilesh Ahuja, Miguel A Lanaspa, Raphael Nemenoff, Zhibin He, Takuji Ishimoto, Pete A Simpson, Mary C Weiser-Evans, Jasna Bacalja, Sarah Faubel
• Journal: American journal of physiology. Renal physiology (Am J Physiol Renal Physiol) Vol. 301 Issue 4 Pg. F907-16 (Oct 2011) ISSN: 1522-1466 [Electronic] United States
• PMID: 21677145 (Publication Type: Journal Article, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't)

Chemical References

• Chemokine CXCL1
• Interleukin-1beta
• Interleukin-6
• Tumor Necrosis Factor-alpha
• Interleukin-10
• Peroxidase

Topics

• Acute Kidney Injury (metabolism)
• Animals
• Capillary Leak Syndrome (metabolism)
• Chemokine CXCL1 (blood)
• Interleukin-10 (biosynthesis, pharmacology)
• Interleukin-1beta (blood)
• Interleukin-6 (blood)
• Kidney (chemistry)
• Liver (chemistry)
• Lung Injury (enzymology, metabolism)
• Mice
• Mice, Inbred C57BL
• Peroxidase (metabolism)
• Reperfusion Injury (metabolism)
• Severity of Illness Index
• Spleen (chemistry)
• Splenectomy (adverse effects)
• Tumor Necrosis Factor-alpha (blood)