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Title: Inflammatory mechanisms in acute pancreatitis
Author: de Beaux, Andrew Charles
Awarding Body: University of Edinburgh
Current Institution: University of Edinburgh
Date of Award: 1997
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On admission to hospital, patients with acute pancreatitis demonstrated increased interleukin-6 and interleukin-8 release but not tumour necrosis factor-α release from isolated PBMCs compared with healthy volunteers. The severity of the disease was not related to the level of cytokine release from a standard cell number. However, the estimated IL-6 and IL-8 release per unit of blood was greater in those patients with severe disease compared with those with mild disease. Severe disease is also characterised by a more prolonged duration of increased pro-inflammatory cytokine release compared with patients with mild disease. Products of the cyclo-oxygenase pathway play a down-regulatory role in PBMCs in patients with acute pancreatitis as indomethacin (a cyclo-oxygenase inhibitor) had no significant effect on pro-inflammatory cytokine release by PBMCs isolated from healthy volunteers, but increased IL-6 and IL-8 release by PBMCs isolated from patients with both mild and severe disease. PBMC pro-inflammatory cytokine release remains sensitive to the down-regulatory action of the T-cell regulatory cytokines, interleukin-4 and interleukin-10. Lymphocyte proliferation is impaired in acute pancreatitis and correlates with the severity of the disease. Following the successful isolation and culture of human umbilical vein endothelial cells, IL-4 and IL-10 (in contrast to their inhibitory action on PBMCs), produce a dose dependent increase in endothelial cell IL-6 and IL-8 release. TNFα is often detectable in patients with acute pancreatitis on admission, even in severe disease. However, elevation in the serum concentration of soluble TNFα receptors would suggest significant TNFα-induced inflammation early in the course of the disease. Glutamine is a conditionally essential amino acid in patients with severe acute pancreatitis and is important for immune function. A double blind, randomised controlled trial of glutamine supplemented versus conventional total parenteral nutrition in patients with severe acute pancreatitis demonstrated a trend towards improved lymphocyte proliferation in the glutamine supplemented group. Furthermore, PBMC IL-8 release but not TNFα and IL-6 release was significantly reduced over the study period.
Supervisor: Not available Sponsor: Not available
Qualification Name: Thesis (M.D.) Qualification Level: Doctoral
EThOS ID:  DOI: Not available