Balance of pro- and anti-inflammatory cytokines in cirrhotic patients undergoing liver transplantation☆
Introduction
Cytokines are a group of endogenous proteins which play a pivotal role in regulating the inflammatory response to surgery through a predictable set of adaptive events. This process, which is designed to maximize the organism's healing potential, is initiated locally, at the site of surgical trauma, by macrophages and monocytes that release pro-inflammatory cytokines. In particular, tumour necrosis factor alpha (TNF-a) and interleukin-1 (IL-1) initiate a cascade of mediators which are directly responsible for the various events associated with inflammation [1], [2], [3], [4], [5], [6]. The increase in the circulating blood of pro-inflammatory cytokines triggers immune cells to release anti-inflammatory cytokines (e.g., IL-10) with the aim of downregulating, through complex feedback mechanisms, the pro-inflammatory process so to maintain homeostasis [1], [2], [3], [4], [5], [6]. From the clinical point of view, the role of circulating inflammatory cytokines is not much clear yet. They might serve as biomarkers for certain clinical events, such as infections (i.e., IL6 in sepsis) or inflammation [7]. In addition, they might serve as marker for metabolic changes or stress [3], [4], [5]. It has been also reported that pre-existing chronic diseases can interact with the patients' capability to set up a balanced inflammatory response to surgery which, therefore, may result in being exaggerated (leading to hyper-inflammation) or inadequate (leading to immunosuppression) possibly causing compromised outcomes and organ dysfunction [2], [3], [7], [8]. In particular, it has been shown that liver cirrhosis leads to an over-expression of various pro- and anti-inflammatory cytokines resulting in a significant derangement of the whole inflammatory response [9], [10], [11], [12]. Therefore, we designed a study to obtain better information about the natural history of serum cytokines in cirrhotic patients undergoing liver transplantation with the aim of assessing if they are still capable to set up an appropriate physiologic relationship between pro-inflammation and anti-inflammation leading to a balanced response to surgery trauma.
Section snippets
Materials and methods
This study involved all of the patients who underwent orthotopic liver transplantation (OLT) at our Centre during 9 consecutive months who gave their informed consent. Anaesthetic and intraoperative management were the same in all cases as previously described [13]. According to the standard protocol at our Centre, a centrifugal pump-driven veno-venous extracorporeal by-pass with heparinised tubing was placed to drain the infra-diaphragmatic venous circulation into the superior vena cava to
Results
Data from 62 of the 67 enrolled patients were analysed (47 males, 15 females). Five patients were excluded because they were transplanted for liver cancer without cirrhosis. Our patients' age was 51.7 ± 8.6 years (range 26–64) and BMI was 24.7 ± 2.2 kg m2. The underlying diseases necessitating liver transplantation were 59 cases of liver cirrhosis (45 viral, 10 alcoholic and 4 cryptogenic) and three of primary biliary cirrhosis. The MELD score of the study population was 19 ± 6.
The studied cytokines
Discussion
Our data show that cirrhotic patients undergoing OLT can have a preserved capability to release cytokines according to a physiological pattern that enables them to restore a balanced relationship between pro-inflammation and anti-inflammation after extensive surgery. This finding is of interest because, as shown by a bulk of research and clinical work, a balanced inflammatory response to surgery almost always results in uneventful recovery whereas a dysregulation of this response predisposes
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No grants and other financial support were used to perform this research.