Cytokine gene expression in peripheral blood mononuclear cells reflects a systemic immune response in alcoholic chronic pancreatitis.
BACKGROUND
Recent data provide evidence of a systemic inflammatory response in severe acute pancreatitis; in contrast, the exact immune mechanisms underlying chronic pancreatitis remain unclear.


METHODS
To investigate the immune response in the clinical features of chronic pancreatitis, we investigated the gene expression of tumor necrosis factor-alpha (TNF-alpha), tumor necrosis factor receptor (TNFR)-p55 and -p75 and inducible nitric oxide synthase (iNOS) in peripheral blood mononuclear cells (PBMC) of 18 patients with late-stage alcoholic chronic pancreatitis of different disease activity (Balthazar criteria).


RESULTS
Semiquantitative reverse transcriptase-polymerase chain reaction revealed a significantly enhanced gene expression of TNF-alpha (P < 0.05), TNFR-p55 (P < 0.05) and TNFR-p75 (P < 0.01) in unstimulated PBMC of patients with advanced chronic pancreatitis (11/18 with calcifications) compared to healthy controls (n = 8). No significant difference was found between patients with mild acute pancreatitis and patients with an inactive quiescent pancreatitis. Moreover, no expression of inducible nitric oxide synthase was detectable.


CONCLUSIONS
The enhanced gene expression of TNFR-p75, TNFR-p55 and TNF-alpha in unstimulated PBMC demonstrates an enhanced leucocyte activation in patients with late-stage chronic pancreatitis and suggests a pathogenetic role of the cytotoxic TNF-alpha pathway in the clinical features of alcoholic chronic pancreatitis. The pathogenetic role of nitric oxide in chronic pancreatitis remains to be fully elucidated.
Hanck
C
C
Department of Medicine IV, University Hospital of Heidelberg at Mannheim, Germany.
Rossol
S
S
Hartmann
A
A
Singer
M V
MV
D000328:Adult; D000917:Antibody Formation; D015703:Antigens, CD / Q000235:genetics; D002908:Chronic Disease; D016207:Cytokines / Q000235:genetics*; D005260:Female; D015870:Gene Expression; D006801:Humans; D008297:Male; D008875:Middle Aged; D009000:Monocytes / Q000502:physiology*; D019512:Pancreatitis, Alcoholic / Q000235:genetics* / Q000276:immunology*; D018124:Receptors, Tumor Necrosis Factor / Q000235:genetics; D047888:Receptors, Tumor Necrosis Factor, Type I; D047889:Receptors, Tumor Necrosis Factor, Type II; D020133:Reverse Transcriptase Polymerase Chain Reaction; D014409:Tumor Necrosis Factor-alpha / Q000235:genetics
D015703:Antigens, CD; D016207:Cytokines; D018124:Receptors, Tumor Necrosis Factor; D047888:Receptors, Tumor Necrosis Factor, Type I; D047889:Receptors, Tumor Necrosis Factor, Type II; D014409:Tumor Necrosis Factor-alpha