Effect of interlukin-10 on serum tumor necrosis factor-alfa and tissues in experimental obstructive jaundi̇ce endotoxemia

Obstructive jaundice is a common clinical manifestation due to extrahepatic bile duct pathologies or pancreatic pathologies. Despite all the advances in surgical techniques, anesthesia, antibiotics used, and preoperative and postoperative patient follow-up in recent years, complications such as sepsis, bleeding disorders, delayed wound healing, and kidney failure in patients with obstructive jaundice make mortality and morbidity high. Many experimental and clinical studies have shown that hypotension, the presence of toxic substances such as bilirubin in the blood, malnutrition, suppressed immune system, and underlying malignancy are predisposing factors for complications seen in patients with obstructive jaundice. However, in clinical and experimental studies conducted in recent years, it has been reported that mortality and morbidity in obstructive jaundice is still high, even when the above mentioned predisposing factors are somehow prevented. Thereupon, studies focused on the real cause of this problem and determined that endotoxemia is directly related to the occurrence of postoperative complications. Prevention of the adverse effects of endotoxin with antiendotoxin treatments has been a proof of the responsibility of endotoxemia for mortality and morbidity in obstructive jaundice. Although the large intestine is an important pool for endotoxins, under normal conditions, they do not cause any harm to our body. However, due to the pathology in obstructive jaundice, the absence of bile flow to the gastrointestinal tract and the decrease in the clearance capacity of Kupffer cells in the liver result in 65% portal and 85% systemic endotoxemia.Many complex and chain reactions are seen in endotoxemia, which is caused by the toxic effects of the bacteria itself or especially the bacterial wall of lipopolysaccharide structure of aerobic Gram (-) bacteria, and various physiological consequences arise with the effect of these. Perhaps the most important physiological outcome is specific shock. Endotoxin is a member of the cytokine-inducing prototypes group . In the presence of endotoxemia, especially in lipopolysaccharide-induced endotoxemia and Sepsis Syndrome, proinflammatory cytokines are released with the activation of the monocyte-macrophage system. Tumor Necrosis Factor-a (TNF-a) is the cytokine that is key among these cytokines, in other words, that initiates events that cause all symptoms of septic shock to emerge. Renal, gastrointestinal and pulmonary problems occur, hypermetabolism is observed, increase in capillary permeability, lactic acidosis, hypotension, and pulmonary hypertension are detected, as in Gram(-) septicemia, in experimental animals or human volunteers administered TNF-a. Many studies have shown that there is a direct correlation between increased serum levels of TNF-a in endotoxemia and multiorgan failure and mortality.factor that inhibits cytokine synthesis (CSIF), that is, interleukin-10 (IL-10). IL-10, released from T helper 2 lymphocyte cells, is a potent inhibitor of inflammation. IL-10 prevents the synthesis of TNF-a in monocytes and tissue macrophages by acting on mRNA expression and gene transcription. It also decreases the synthesis of IL-1, IL-6, IL-8. Recently, attention has been turned to IL-10 for its very important effects. In patients with obstructive jaundice, endotoxemia is observed as explained above due to the natural course of the disease, and infectious conditions such as cholangitis frequently occur in these patients by making many preoperative interventions. The aim of this study is to demonstrate the effects of IL-10 on serum TNF-a levels and tissues following experimental endotoxemia in an obstructive jaundice model that has not been studied before. IL-10 can prevent the negative consequences of endotoxemia by acting on cytokines. This research may lead to the emergence of new approaches in the treatment of obstructive jaundice by reducing the high mortality and morbidity rates.