title: Cross-talk between innate cytokines and the pancreatic polypeptide family in acute pancreatitis.
abstract: Low-grade inflammation persists in patients with acute pancreatitis (AP) after hospital discharge, and is linked to metabolic disorders. Neuropeptide Y (NPY) is well recognized as an important mediator of inflammation in these patients but the role of the other two structurally similar peptides, pancreatic polypeptide (PP) and peptide YY (PYY), in inflammation has been sparsely investigated. The aim was to investigate the association between PYY, PP, NPY and circulating levels of innate cytokines in patients after AP.
  
  
  
  Fasting blood samples were collected to measure PYY (ng/mL), PP (ng/mL), NPY (pg/mL), interleukin-6 (IL-6) (ng/mL), monocyte chemoattractant protein (MCP) 1 (ng/mL), and tumour necrosis factor (TNF) α (ng/mL). Modified Poisson regression analysis and linear regression analyses were conducted. Age, sex, ethnicity, obesity, diabetes, aetiology, time from 1st attack of AP, recurrence, severity, physical activity, and smoking were adjusted for in several statistical models. P<0.05 was considered statistically significant.
  
  
  
  A total of 93 patients were recruited. Peptide YY was significantly associated (p<0.001) with IL-6, MCP-1, and TNFα in the unadjusted and all adjusted models. Pancreatic polypeptide was significantly associated (p<0.001) with IL-6, MCP-1, and TNFα in the unadjusted and at least one adjusted model. Peptide YY and PP together contributed 22.2%, 72.7%, and 34.6% to the variance of IL-6, MCP-1, and TNFα, respectively. Neuropeptide Y was not significantly associated with any of the three cytokines.
  
  
  
  Peptide YY and PP are associated with circulating innate pro-inflammatory cytokines in patients after AP and cumulatively contribute to nearly half of the variance of IL-6, MCP-1, and TNFα. Future research is warranted to investigate the signaling pathways that underlie these associations.
authors.affiliation: Department of Surgery, University of Auckland, Auckland, New Zealand. Electronic address: s.pendharkar@auckland.ac.nz.
authors.forename: Sayali A
authors.initials: SA
authors.lastname: Pendharkar
authors.affiliation: Department of Surgery, University of Auckland, Auckland, New Zealand. Electronic address: ruma.singh@auckland.ac.nz.
authors.forename: Ruma G
authors.initials: RG
authors.lastname: Singh
authors.affiliation: Department of Surgery, University of Auckland, Auckland, New Zealand. Electronic address: max.petrov@gmail.com.
authors.forename: Maxim S
authors.initials: MS
authors.lastname: Petrov
mesh_terms: D000208:Acute Disease; D000328:Adult; D000368:Aged; D016207:Cytokines / Q000097:blood* / Q000276:immunology; D005215:Fasting / Q000097:blood; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D007113:Immunity, Innate; D008297:Male; D008875:Middle Aged; D009478:Neuropeptide Y / Q000097:blood* / Q000276:immunology; D010191:Pancreatic Polypeptide / Q000097:blood* / Q000276:immunology; D010195:Pancreatitis / Q000097:blood* / Q000276:immunology / Q000628:therapy; D019894:Peptide YY / Q000097:blood* / Q000276:immunology
chemical_list: D016207:Cytokines; D009478:Neuropeptide Y; D019894:Peptide YY; D010191:Pancreatic Polypeptide
keywords: Acute pancreatitis; Interleukin-6; Low-grade inflammation; MCP-1; Pancreatic polypeptide family; TNFα