Up-regulation of Fas ligand (FasL) mRNA expression in peripheral blood mononuclear cells (PBMC) after major surgery

Abstract

FasL, which is expressed mainly on activated lymphocytes, can induce apoptosis (programmed cell death) of cells which express Fas. Fas/FasL interaction is primarily beneficial in maintaining immunological and physiological homeostasis by eliminating unnecessary cells. Dysregulation of the interaction, however, leads to tissue damage. We investigated how Fas/FasL levels changed after major surgery. The major aim of this study was to elucidate the involvement of the Fas/FasL system in postoperative inflammation. The investigation involved 10 patients admitted to the intensive care unit after surgery. Although the percentage of Fas+ cells and the amount of Fas expression tended to increase, there was no significant difference between pre- and post-operative samples. In contrast, the levels of FasL mRNA were dramatically up-regulated after operation. Post-operative C-reactive protein (CRP) levels increased and correlated well with FasL levels (r=0.91, P<0.01). Lymphocyte counts decreased after operation and were inversely proportional to FasL levels (r=0.58, P < 0.05). These results suggest that the enhanced FasL expression is likely to be related to systemic inflammatory responses induced during the perioperative period. FasL up-regulation may be involved in the aggravation of tissue damage, including lymphocytopenia, in the early post-operative period.

Lymphocyte apoptosis after major abdominal surgery is not influenced by anesthetic technique: a comparative study of general anesthesia versus combined general and epidural analgesia

“…Activation of the apoptotic death program is thought to be a crucial mechanism, responsible for the lymphocyte depletion and immune suppression frequently seen in surgical patients immediately after surgery [2,11]. Surgeryinduced lymphocytopenia may be caused by lymphocyte redistribution, inappropriate cell death, or both [12,13]. Delogu et al showed that the rate of lymphocyte apoptosis is significantly increased in patients undergoing surgical stress [4].…”

Applications and Limitations of Blood Eosinophilia for the Diagnosis of Acute Cellular Rejection in Liver Transplantation

“…There are several possible reasons for the low sensitivity of blood eosinophilia in the detection of ACR: Firstly, corticosteroids administered immediately following transplantation, and used for the treatment of ACR, are known to be eosinopenic (6), and these effects may be prolonged in patients with renal or hepatic insufficiency. Secondly, defects in cellular immunity associated with severe liver dysfunction (15), acute severe illness and major abdominal surgery (16) may suppress the eosinophil count in the presence of ACR. Thirdly, we show that blood eosinophilia is a particularly poor marker of ACR in the setting of hepatitis C virus infection and hypothesize that HCV may suppress the eosinophilic response (see later); it is therefore plausible that other viral infections such as hepatitis B virus, cytomegalovirus and herpes simplex virus may have similar suppressive effects on the eosinophil count and limit the sensitivity in the detection of ACR.…”

Apoptosis in Lymphocytes of Pancreatic Cancer Patients: Influence of Preoperative Enteral Immunonutrition and Extensive Surgery

“…Such lymphocyte phenotypes and a significantly decreased Bcl-2 intracellular expression after surgery (significant on day 1 and 7) for pancreatic cancer may lead to an inappropriate cell apoptosis. A series of studies has demonstrated that circulating lymphocytes in the early postoperative period are susceptible to apoptosis, which may cause deletion of peripheral lymphocytes after surgery (Oka et al 1996;Sugimoto et al 1998). In the early postoperative period, surgical trauma under general anesthesia induces an intracellular perturbation on peripheral lymphocytes, resulting in both up-regulation of death-signaling factors (Fas, FasL) and down-regulation of survivalsignaling factors (Bcl-2).…”