Cytokine regulation of constitutive production of interleukin-8 and -6 by human pancreatic cancer cell lines and serum cytokine concentrations in patients with pancreatic cancer.
Patients with pancreatic cancer frequently demonstrate symptoms such as weight-loss and muscle wasting and have clinical evidence of a systemic inflammatory response. Such effects may be mediated by pro-inflammatory cytokines derived from tumor cells. The production of interleukin-6 and -8 by pancreatic cancer cell lines and the influence of other cytokines on this production was studied. IL-8 was produced by all cell lines and production was increased following exposure to IL-1 and TNF. Cytokine-stimulated, but not basal IL-8 production was reduced by co-incubation with IL-4 in the MIA PaCa-2 and PANC-1 cell lines. The CFPAC cell line produced IL-6, but this production was not altered by IL-1, TNF or IL-4. In the PANC-1 cell line IL-8 and IL-8 receptors were only detected by PCR in cells which had been stimulated with TNF or IL-1. Serum concentrations of IL-6 and IL-8 were elevated in patients with pancreatic cancer compared with controls. In conclusion, human pancreatic cancer cell lines elaborate pro-inflammatory cytokines which have the potential to mediate elements of the systemic inflammatory response.
Wigmore
S J
SJ
Department of Clinical and Surgical Sciences (Surgery), University of Edinburgh, Royal Infirmary of Edinburgh, Lauriston Place, Edinburgh, EH3 9YW, UK.
Fearon
K C H
KC
Sangster
K
K
Maingay
J P
JP
Garden
O J
OJ
Ross
J A
JA
D000368:Aged; D002097:C-Reactive Protein / Q000096:biosynthesis; D016207:Cytokines / Q000378:metabolism*; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D007249:Inflammation; D007375:Interleukin-1 / Q000494:pharmacology; D015847:Interleukin-4 / Q000494:pharmacology; D015850:Interleukin-6 / Q000096:biosynthesis*; D016209:Interleukin-8 / Q000096:biosynthesis*; D008297:Male; D008875:Middle Aged; D010190:Pancreatic Neoplasms / Q000097:blood* / Q000378:metabolism* / Q000473:pathology; D016133:Polymerase Chain Reaction; D012313:RNA / Q000378:metabolism; D014407:Tumor Cells, Cultured; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology
D016207:Cytokines; D007375:Interleukin-1; D015850:Interleukin-6; D016209:Interleukin-8; D014409:Tumor Necrosis Factor-alpha; D015847:Interleukin-4; D012313:RNA; D002097:C-Reactive Protein