Isolation of interstitial fluid and demonstration of local proinflammatory cytokine production and increased absorptive gradient in chronic peritoneal dialysis

Abstract

In peritoneal dialysis (PD) patients, the frequent exposure to "unphysiological" dialysis fluids elicits a chronic state of a low-grade peritoneal inflammation leading to interstitial matrix remodeling and angiogenesis. Proinflammatory cytokines are important regulators involved in this inflammatory process that ultimately leads to dysfunction of the peritoneum as a dialysis membrane. We aimed to measure the local concentrations of proinflammatory cytokines in the peritoneal interstitial fluid (IF). Furthermore, we wanted to assess how the driving forces for fluid and solute exchanges are affected in a remodeled interstitial matrix and thus measured the colloid osmotic pressure (COP) gradient in rats that were exposed to chronic PD. After 8 wk of peritoneal dialysis, IF from peritoneum was isolated using a centrifugation method, and was analyzed for cytokine content and COP along with plasma. For several of the proinflammatory cytokines there were gradients from IF to plasma, showing local production. For some cytokines, the concentration in IF was increased severalfold, whereas IL-18 was increased systemically due to PD. Furthermore, the presence of the catheter per se seemed to increase cytokine levels. COP in IF was significantly decreased in the PD group, while collagen and hyaluronan content was increased. Collectively, our data suggest that the increased levels of proinflammatory cytokines after PD may be an integral component of the development of fibrosis and angiogenesis commonly seen in PD patients, and the decreased COP in IF after chronic PD may shift the Starling equilibrium across peritoneal capillaries to an absorptive state.

Rhein, a Natural Anthraquinone Derivative, Attenuates the Activation of Pancreatic Stellate Cells and Ameliorates Pancreatic Fibrosis in Mice with Experimental Chronic Pancreatitis

“…The LTC-14 cells also responded to pro-inflammatory cytokine TNF-α and led to elevated expression levels of Acta2 and Tgf-β ; therefore, pro-inflammatory cytokines such as TNF-α do play important roles in fibrotic events. Our results are in accordance to recent reports that the levels of pro-inflammatory cytokines positively correlate to the severity of fibrosis [47,48]. At the molecular level, the repairing machinery for the injured or inflamed parenchyma creates a microenvironment that provides pro-regeneratory effects and simultaneously promotes the production of various pro-fibrotic factors in large amounts in which fibrogenesis is elicited.…”

Update on Inflammation in Chronic Kidney Disease

“…Other modifiers originate from the genetic background, as well as from the diet, life-style and environment, representing epigenetic influences. Decreased renal clearance clearly accounts for higher levels of circulating cytokines, although increased production has also been described [40]. Uremic milieu produces oxidative stress [41] and carbonyl stress [42] that are highly pro-inflammatory.…”

Does inflammation affect outcomes in dialysis patients?

“…Multiple factors likely contribute to chronic inflammatory activation in kidney disease patients (Figure ). With declining renal function, both decreased renal clearance, as well as increased production, contribute to higher levels of circulating cytokines . The uremic milieu also promotes oxidative stress and carbonyl stress, both of which are highly proinflammatory.…”