Plasma Sphingolipids in Acute Pancreatitis

Abstract

Acute pancreatitis (AP) is a prevalent gastrointestinal disorder associated with systemic inflammatory response syndrome and, in the case of severe AP, a mortality rate ranging from 36% to 50%. Standard clinical treatment of AP includes intensive hydration, analgesia, and management of complications. Unfortunately, the direct treatment of AP at the level of its molecular pathomechanism has not yet been established. Recent studies indicate that the sphingolipid signaling pathway may be one of the important factors contributing to the development of inflammation in pancreatic diseases. In the current study, we sought to investigate this promising route. We examined the plasma sphingolipid profile of 44 patients with acute pancreatitis, dividing them into three groups: mild, moderate and severe AP. Samples were collected from these groups at days 1, 3 and 7 following their hospital admission. We demonstrated significant changes in blood plasma sphingolipids in relation to the time course of AP. We also found an inhibition of de novo ceramide synthesis in mild and moderate AP. However, the most important and novel finding was a significant elevation in sphingosine-1-phosphate (S1P) (a downstream metabolite of ceramide) in mild AP, as well as a dramatic reduction in the lipid molecule content in the early stage (days 1 and 3) of severe AP. This strongly indicates that plasma S1P could serve as a prognostic marker of AP severity.

Impact of Acute Pancreatic Injury on Sphingolipid Metabolism in the Salivary Glands

“…These observations were recently confirmed in a study published by Konończuk et al Briefly, in the rodent model of AP, it was noted that S1P concentration in pancreatic tissue samples was considerably elevated compared to the control group [11]. A similar increment was observed in the centrifuged plasma of patients with a severe form of AP [10]. Interestingly, S1P synthetic analogue, fingolimod, may represent a novel therapeutic strategy in preventing AP and its complications [32,33].…”

“…However, the pathogenesis of AP and T1DM has not been thoroughly explained. It is believed that one of its possible factors may be alterations in sphingolipid metabolism, which has been recently proven in both human and animal models [10,11].…”

Sphingosine‐1‐phosphate in acute exercise and training

“…It is well established that strong activation of inflammatory pathways results in a profound reduction in plasma S1P concentration. Such effect was observed in patients with sepsis, acute pancreatitis, and dengue infection, as well as following lipopolysaccharide administration to mice 35‐38 . It is, therefore, possible that activation of the inflammatory response contributes to decreased S1P level during ultra‐endurance effort.…”

Evaluation of tissue trauma and healing on the basis of tumour necrosis factor-alpha, interleukin-6, and C-reactive protein in peripheral blood during and after pyometra in bitches

“…However, dysregulated cytokine signalling associated with LPS and/or sepsis can result in autoimmunity (6), cytokine storm, SIRS, septic shock, multiple organ dysfunction syndrome (MODS) and death (1,4,13,27). The duration of SIRS also determines the risk of developing MODS (14).…”