Effect of interleukin-2 on peripheral blood mononuclear cell cytokine production and the hepatic acute phase protein response.
This study investigated the ability of recombinant interleukin-2 (IL-2) to modulate the ability of peripheral blood mononuclear cells (PBMCs) to stimulate an acute phase protein response in isolated human hepatocytes. The effect of IL-2 on the production of tumour necrosis factor-alpha (TNF) and interleukin-6 (IL-6) by PBMCs isolated from patients with gastrointestinal cancer, multiple organ failure, and healthy controls was also studied. The ability of supernatants from IL-2-treated PBMCs to elicit an acute phase response in hepatocytes was then investigated. IL-2 had no effect on IL-6 or TNF production by PBMCs isolated from any group in the presence or absence of bacterial lipopolysaccharide (LPS). Despite this, preincubation of PBMCs with IL-2 significantly reduced the potential of LPS-stimulated PBMC supernatants to stimulate production of alpha1 antichymotrypsin, alpha1-acid glycoprotein, and C-reactive protein by hepatocytes. These observations were not due to a direct effect of IL-2 on hepatocyte acute phase protein production. These findings suggest that in this model IL-2 may modulate PBMC-induced acute phase protein production through an IL-6 and TNF-independent pathway.
Wigmore
S J
SJ
University Department of Surgery, Royal Infirmary of Edinburgh, Lauriston Place, Edinburgh, United Kingdom.
Fearon
K C H
KC
Maingay
J P
JP
Garden
O J
OJ
Ross
J A
JA
D000209:Acute-Phase Proteins / Q000032:analysis / Q000096:biosynthesis*; D000328:Adult; D002097:C-Reactive Protein / Q000032:analysis / Q000096:biosynthesis; D002478:Cells, Cultured; D003470:Culture Media; D016207:Cytokines / Q000032:analysis / Q000096:biosynthesis*; D005260:Female; D005770:Gastrointestinal Neoplasms / Q000097:blood / Q000276:immunology; D006801:Humans; D007376:Interleukin-2 / Q000494:pharmacology*; D015850:Interleukin-6 / Q000032:analysis / Q000096:biosynthesis; D007963:Leukocytes, Mononuclear / Q000187:drug effects* / Q000276:immunology; D008070:Lipopolysaccharides; D008099:Liver / Q000276:immunology*; D008297:Male; D008875:Middle Aged; D009102:Multiple Organ Failure / Q000097:blood / Q000276:immunology; D009961:Orosomucoid / Q000032:analysis / Q000096:biosynthesis; D011994:Recombinant Proteins / Q000494:pharmacology; D014409:Tumor Necrosis Factor-alpha / Q000032:analysis / Q000096:biosynthesis; D000514:alpha 1-Antichymotrypsin / Q000032:analysis / Q000096:biosynthesis
D000209:Acute-Phase Proteins; D003470:Culture Media; D016207:Cytokines; D007376:Interleukin-2; D015850:Interleukin-6; D008070:Lipopolysaccharides; D009961:Orosomucoid; D011994:Recombinant Proteins; D014409:Tumor Necrosis Factor-alpha; D000514:alpha 1-Antichymotrypsin; D002097:C-Reactive Protein