Decreased interleukin-2 production in murine acute pancreatitis: potential for immunomodulation.
OBJECTIVE
The role of the cytokine interleukin 2 (IL-2) has long been recognized as central to normal immunologic function and defense against infection after burns and trauma, but little effort has been directed towards its role in acute pancreatitis (AP), which also has a high mortality related to sepsis. This study investigated the potential role of IL-2 in mice with diet-induced AP.


METHODS
AP was induced in mice by 10 days of feeding a choline-deficient, ethionine-supplemented diet. T-helper (CD4) cells were estimated, and T-cell mitogen-stimulated splenocyte proliferation and IL-2 production in vitro were measured on days 3, 7, and 10.


RESULTS
Significant reduction in IL-2 production was found on day 3 (32%; P < 0.05) and day 10 (48%; P < 0.005). Administration of intraperitoneal lipopolysaccharide on day 10 was associated with reduced IL-2 production (P < 0.025) 4 hours later and 90% mortality in animals with AP. In vivo therapy with recombinant IL-2 improved in vitro IL-2 secretion (P < 0.05) and reduced lipopolysaccharide-induced mortality (P = 0.036).


CONCLUSIONS
Murine diet-induced AP is associated with impaired immune function and increased susceptibility to sepsis and may be a valuable tool in the investigation of immunomodulation in AP.
Curley
P
P
Department of Surgery, Brigham and Women's Hospital, Boston, Massachusetts, USA.
Nestor
M
M
Collins
K
K
Saporoschetz
I
I
Mendez
M
M
Mannick
J A
JA
Rodrick
M L
ML
D000208:Acute Disease; D000276:Adjuvants, Immunologic; D000818:Animals; D018791:CD4 Lymphocyte Count; D004731:Endotoxins / Q000009:adverse effects; D005260:Female; D007376:Interleukin-2 / Q000096:biosynthesis* / Q000627:therapeutic use; D008070:Lipopolysaccharides / Q000009:adverse effects; D008213:Lymphocyte Activation; D051379:Mice; D008815:Mice, Inbred Strains; D010195:Pancreatitis / Q000276:immunology* / Q000378:metabolism / Q000628:therapy; D011994:Recombinant Proteins / Q000627:therapeutic use; D013601:T-Lymphocytes / Q000276:immunology / Q000378:metabolism
D000276:Adjuvants, Immunologic; D004731:Endotoxins; D007376:Interleukin-2; D008070:Lipopolysaccharides; D011994:Recombinant Proteins