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Expression of interleukin 8 (IL-8) and substance P in human chronic pancreatitis
  1. P Di Sebastianoa,b,
  2. F F di Molaa,c,
  3. C Di Febbod,
  4. G Baccanted,
  5. E Porrecad,
  6. P Innocentic,
  7. H Friessa,
  8. M W Büchlera
  1. aDepartment of Visceral and Transplantation Surgery, University of Bern, Inselspital, Switzerland, bDepartment of Surgery, Bozen General Hospital, Bozen, Italy, cSurgical Unit, G D'Annunzio University, Chieti, Italy, dDepartment of Internal Medicine, G D'Annunzio University, Chieti, Italy
  1. Dr H Friess, Department of Visceral and Transplantation Surgery, University of Bern, Inselspital, CH-3010 Bern, Switzerland. Email: helmut.friess{at}


BACKGROUND Changes in substance P content and a relationship between the degree of perineural inflammation and pain has been demonstrated in chronic pancreatitis. Whether a relationship exists between neural alteration and pancreatic inflammation (neurogenic inflammation) is not known.

AIMS In the present study we evaluated gene expression of preprotachykinin A (PPT-A), the gene encoding substance P, and interleukin 8, a proinflammatory and hyperalgesic mediator whose release is co-regulated by substance P.

PATIENTS Pancreatic tissue specimens obtained from 21 patients (16 male, five female) with chronic pancreatitis and 18 healthy organ donors (nine male, nine female) were analysed.

METHODS Gene expression of PPT-A and interleukin 8 was studied by northern blot analysis. Respective proteins were localised using immunohistochemistry.

RESULTS Northern blot analysis showed that PTT-A mRNA expression levels were present at comparable levels in normal and chronic pancreatitis tissue samples. In contrast, interleukin 8 mRNA was expressed at very low levels in normal controls but was increased 41-fold (p<0.001) in chronic pancreatitis tissue samples. Using immunohistochemistry, interleukin 8 protein was localised mainly in immune cells often found around enlarged pancreatic nerves. In addition, in chronic pancreatitis, intense interleukin 8 immunostaining was present in metaplastic ductal cells of the atrophic pancreatic parenchyma. In chronic pancreatitis samples there was a positive relationship between interleukin 8 mRNA levels and the presence of ductal metaplasia (r=0.795; p<0.001) and the inflammation score (r=0.713; p<0.001).

CONCLUSIONS Our data indicate that in chronic pancreatitis, the increase in substance P in enlarged pancreatic nerves is not caused by enhanced intrapancreatic PTT-A mRNA expression, suggesting that the location of substance P synthesis is outside of the pancreas. In addition, localisation of interleukin 8 positive immune cells around pancreatic nerves further supports the existence of neuroimmune interactions as a pathophysiological mechanism in chronic pancreatitis.

  • chronic pancreatitis
  • interleukin 8
  • neurogenic inflammation
  • preprotachykinin A
  • substance P
  • immunohistochemistry
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  • Abbreviations used in this paper:
    interleukin 8
    preprotachykinin A
    chronic pancreatitis
    enteric nervous system
    glyceraldehyde-3-phosphate dehydrogenase
    Tris buffered saline
    polymorphonuclear leucocytes
    tumour necrosis factor

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