Endotoxin, cellular immune dysfunction and acute pancreatitis.
Clinical similarities between the sepsis syndrome seen in severe acute pancreatitis (AP) and that seen after burns, postoperative infection and trauma led to a series of investigations to elucidate the nature of immunological compromise in cases of severe AP. Significant alterations in lymphocyte surface marker antigen expression were demonstrated with reduced total T-lymphocyte (CD3), T-helper (CD4) and T-suppressor (CD8) cell numbers (P < 0.001, Mann-Whitney U test) during the acute phase of severe attacks compared with mild attacks. These abnormalities were reversible with increased CD3 (P < 0.005, Student's t test), CD4 (P < 0.01) and CD8 (P < 0.05) numbers in the convalescent phase of severe attacks. Experiments with a murine model of acute pancreatitis demonstrated further cellular immune abnormalities in AP as have previously been documented in models of burn, trauma and sepsis. Decreased interleukin-2 production by mononuclear cells (P < 0.005) was associated with susceptibility to endotoxin challenge. Immunomodulatory therapy in the form of exogenous IL-2 therapy or with induction of endotoxin tolerance not only led to increased IL-2 production (P < 0.01) but also to significantly reduced mortality after endotoxin exposure compared with control animals (P < 0.05, Wilcoxon-Gehan statistic). Cellular immune dysfunction in acute pancreatitis is seen in humans and in a murine model; it is associated with endotoxin exposure and with susceptibility to the deleterious effects of endotoxin and can be partially reversed by exogenous IL-2 therapy and by induction of endotoxin tolerance.
Curley
P J
PJ
Royal College of Surgeons of England, London.
D000208:Acute Disease; D000818:Animals; D004322:Drainage; D004731:Endotoxins / Q000097:blood*; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D007111:Immunity, Cellular; D007376:Interleukin-2 / Q000627:therapeutic use; D015850:Interleukin-6 / Q000097:blood; D008070:Lipopolysaccharides / Q000276:immunology; D018655:Lymphocyte Count; D051379:Mice; D010195:Pancreatitis / Q000097:blood / Q000276:immunology* / Q000628:therapy; D016176:T-Lymphocyte Subsets / Q000276:immunology*
D004731:Endotoxins; D007376:Interleukin-2; D015850:Interleukin-6; D008070:Lipopolysaccharides