Role of Interleukin 6 in Acute Pancreatitis: A Possible Marker for Disease Prognosis

Abstract

Acute pancreatitis (AP) is a significant cause of morbidity, even in children, and is frequently associated with systemic manifestations. There are many cytokines involved in the inflammatory response characteristic of this disease. Interleukin 6 (IL-6) is one of the most important cytokines involved in AP, beginning from cellular injury and continuing to the systemic inflammatory response and distant organ involvement. IL-6 is a multifunctional cytokine that regulates acute-phase response and inflammation. It is produced by various cells and exerts its biological role on many cells through its high-affinity complex receptor. IL-6 has been investigated as a predicting maker for severe forms of AP. Many studies have validated the use of IL-6 serum levels in the first 48 h as a reliable marker for severe evolution and multisystemic involvement. Still, it has not been used in daily practice until now. This review discusses the main binding mechanisms by which IL-6 triggers cellular response and the AP pathogenetic mechanisms in which IL-6 is involved. We then emphasize the promising role of IL-6 as a prognostic marker, which could be added as a routine marker at admission in children with AP.

Keywords: IL-6; acute pancreatitis; biomarker; prognosis; severity.

Figure 1

(A): The IL-6 signaling. The classic pathway can be activated on cells that express both IL-6R and gp130. The trans-signaling pathway occurs through a soluble form of IL-6R that binds IL-6 and forms a complex that can act on cells that lack the IL-6R but express gp130. Both pathways activate the JAK/STAT3 cascade. (B): The involvement of IL-6 in AP pathogenesis. IL-6 is released by the necrotic acinar cells, triggers the recruitment of inflammatory cells in the pancreas (neutrophils, monocytes, T lymphocytes), and activates the resident macrophages. IL-6 also determines the activation of Th1 and Th17 cells.