Heat shock factor-1 and nuclear factor-kappaB are systemically activated in human acute pancreatitis.
BACKGROUND
Nuclear factor-kappa B (NF-kappaB) is a transcription factor for a wide range of proinflammatory mediators while heat shock factor-1 (HSF-1) transcribes stress proteins that protect against cellular damage. Both are attractive therapeutic targets, undergoing investigation in other acute inflammatory conditions, such as sepsis.


OBJECTIVE
To evaluate the role of the transcription factors NF-kappaB and HSF-1 in human acute pancreatitis and their relationship to cytokine/chemokine production, disease severity and outcome.


METHODS
Twenty-four patients with acute pancreatitis and 12 healthy controls.


METHODS
Peripheral blood mononuclear cells were isolated. NF-kappaB and HSF-1 were measured by electrophoretic mobility shift assay. Soluble tumor necrosis factor (TNF) receptor II and interleukin-8 were measured by ELISA. Acute physiology scores (APS), APACHE II scores and final Atlanta designations of severity were also determined.


RESULTS
Systemic NF-kappaB activation occurs in acute pancreatitis compared to healthy controls (P=0.004). However, there was no significant difference between those with mild and severe disease (P=0.685). Systemic activation of HSF-1 was observed in acute pancreatitis compared to healthy controls although this did not reach statistical significance (P=0.053). Activation, however, was greatest in those who had a final Atlanta designation of mild pancreatitis compared to those who had a severe attack of acute pancreatitis (P=0.036). Furthermore, HSF-1 was inversely correlated with acute physiology score (APS; r=-0.49, P=0.019) and APACHE II score (r=-0.47, P=0.026).


CONCLUSIONS
Both NF-kappaB and HSF-1 are systemically activated in human acute pancreatitis. HSF-1 activation may protect against severity of pancreatitis.
O'Reilly
Derek A
DA
Department of Surgery, Derriford Hospital, Plymouth, United Kingdom. doreilly@doctors.org.uk
Roberts
Jonathan R
JR
Cartmell
Mark T
MT
Demaine
Andrew G
AG
Kingsnorth
Andrew N
AN
D000208:Acute Disease; D015415:Biomarkers / Q000097:blood; D002467:Cell Nucleus / Q000378:metabolism; D018925:Chemokines / Q000096:biosynthesis; D016207:Cytokines / Q000096:biosynthesis; D004268:DNA-Binding Proteins / Q000097:blood*; D000076249:Heat Shock Transcription Factors; D006801:Humans; D016209:Interleukin-8 / Q000097:blood; D007963:Leukocytes, Mononuclear / Q000378:metabolism; D016328:NF-kappa B / Q000097:blood*; D010195:Pancreatitis / Q000097:blood* / Q000175:diagnosis*; D047889:Receptors, Tumor Necrosis Factor, Type II / Q000097:blood; D012016:Reference Values; D014157:Transcription Factors / Q000097:blood*
D015415:Biomarkers; D018925:Chemokines; D016207:Cytokines; D004268:DNA-Binding Proteins; D000076249:Heat Shock Transcription Factors; D016209:Interleukin-8; D016328:NF-kappa B; D047889:Receptors, Tumor Necrosis Factor, Type II; D014157:Transcription Factors