Browsing by Author "Kiekhaefer, Carol M."

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    Circulating IL-6 upregulates IL-10 production in splenic CD4 + T cells and limits acute kidney injury-induced lung inflammation
    (Elsevier, 2017-05) Andres-Hernando, Ana; Okamura, Kayo; Bhargava, Rhea; Kiekhaefer, Carol M.; Soranno, Danielle E.; Kirkbride-Romeo, Lara A.; Gil, Hyo-wook; Altmann, Chris; Faubel, Sarah; Pediatrics, School of Medicine
    Although it is well established that acute kidney injury (AKI) is a proinflammatory state, little is known about the endogenous counter-inflammatory response. IL-6 is traditionally considered a pro-inflammatory cytokine that is elevated in the serum in both human and murine AKI. However, IL-6 is known to have anti-inflammatory effects. Here we sought to investigate the role of IL-6 in the counter-inflammatory response after AKI, particularly in regard to the anti-inflammatory cytokine IL-10. Ischemic AKI was induced by bilateral renal pedicle clamping. IL-10-deficient mice had increased systemic and lung inflammation after AKI, demonstrating the role of IL-10 in limiting inflammation after AKI. We then sought to determine whether IL-6 mediates IL-10 production. Wild-type mice with AKI had a marked upregulation of splenic IL-10 that was absent in IL-6-deficient mice with AKI. In vitro, addition of IL-6 to splenocytes increased IL-10 production in CD4+ T cells, B cells, and macrophages. In vivo, CD4-deficient mice with AKI had reduced splenic IL-10 and increased lung myeloperoxidase activity. Thus, IL-6 directly increases IL-10 production and participates in the counter-inflammatory response after AKI.
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    Early peritoneal dialysis reduces lung inflammation in mice with ischemic acute kidney injury
    (Elsevier, 2017-08) Altmann, Chris; Ahuja, Nilesh; Kiekhaefer, Carol M.; Andres Hernando, Ana; Okamura, Kayo; Bhargava, Rhea; Duplantis, Jane; Kirkbride-Romero, Lara A.; Huckles, Jill; Fox, Benjamin M.; Kahn, Kashfi; Soranno, Danielle E.; Gil, Hyo-wook; Teitelbaum, Isaac; Faubel, Sarah; Pediatrics, School of Medicine
    Although dialysis has been used in the care of patients with acute kidney injury (AKI) for over 50 years, very little is known about the potential benefits of uremic control on systemic complications of AKI. Since the mortality of AKI requiring renal replacement therapy (RRT) is greater than half in the intensive care unit, a better understanding of the potential of RRT to improve outcomes is urgently needed. Therefore, we sought to develop a technically feasible and reproducible model of RRT in a mouse model of AKI. Models of low- and high-dose peritoneal dialysis (PD) were developed and their effect on AKI, systemic inflammation, and lung injury after ischemic AKI was examined. High-dose PD had no effect on AKI, but effectively cleared serum IL-6, and dramatically reduced lung inflammation, while low-dose PD had no effect on any of these three outcomes. Both models of RRT using PD in AKI in mice reliably lowered urea in a dose-dependent fashion. Thus, use of these models of PD in mice with AKI has great potential to unravel the mechanisms by which RRT may improve the systemic complications that have led to increased mortality in AKI. In light of recent data demonstrating reduced serum IL-6 and improved outcomes with prophylactic PD in children, we believe that our results are highly clinically relevant.