Effect of interleukin-4 on pro-inflammatory cytokine production and the acute phase response in healthy individuals and in patients with cancer or multiple organ failure.
1. This study investigates whether previously documented effects of interleukin-4 in down-regulating pro-inflammatory cytokine production by peripheral blood mononuclear cells (PBMCs) from healthy individuals would be reproducible in PBMCs isolated from patients with multiple organ failure (acute disease model) and gastrointestinal cancer (chronic disease model). The effects of interleukin-4 on the ability of PBMC supernatants to elicit an acute phase protein response from isolated human hepatocytes were also studied. 2. Incubation of PBMCs with interleukin-4 significantly reduced both spontaneous and lipopolysaccharide-induced production of tumour necrosis factor and lipopolysaccharide-induced interleukin-6 production, demonstrating that the PBMCs from patients with acute and chronic disease are not refractory to the effects of interleukin-4. The effects of interleukin-4 on the ability of PBMCs from the groups studied to elicit an acute phase response were complex and varied both between patient groups and individual acute phase proteins. Overall, interleukin-4 reduced the potential of PBMCs to stimulate production of the positive acute phase proteins C-reactive protein, alpha1-antichymotrypsin and alpha1-acid glycoprotein.3. This work emphasizes the pleiotropic nature of cytokines and the complex regulatory mechanisms which exist. The study illustrates the difficulties in devising in vivo intervention strategies using cytokines such as interleukin-4.
Wigmore
S J
SJ
Molecular Immunology Group, Lister Research Laboratories, University Department of Surgery, Royal Infirmary of Edinburgh, Edinburgh EH3 9YW, U.K.
Maingay
J P
JP
Fearon
K C
KC
O'Riordain
M G
MG
Ross
J A
JA
D000210:Acute-Phase Reaction / Q000276:immunology*; D002097:C-Reactive Protein / Q000096:biosynthesis; D002478:Cells, Cultured; D003864:Depression, Chemical; D005770:Gastrointestinal Neoplasms / Q000276:immunology; D006801:Humans; D015847:Interleukin-4 / Q000494:pharmacology*; D015850:Interleukin-6 / Q000096:biosynthesis*; D007963:Leukocytes, Mononuclear / Q000187:drug effects / Q000276:immunology*; D008070:Lipopolysaccharides / Q000494:pharmacology; D008099:Liver / Q000276:immunology; D018448:Models, Immunological; D009102:Multiple Organ Failure / Q000276:immunology; D009961:Orosomucoid / Q000096:biosynthesis; D011228:Prealbumin / Q000096:biosynthesis; D011994:Recombinant Proteins / Q000494:pharmacology; D014168:Transferrin / Q000096:biosynthesis; D014409:Tumor Necrosis Factor-alpha / Q000096:biosynthesis*; D000514:alpha 1-Antichymotrypsin / Q000096:biosynthesis
D015850:Interleukin-6; D008070:Lipopolysaccharides; D009961:Orosomucoid; D011228:Prealbumin; D011994:Recombinant Proteins; D014168:Transferrin; D014409:Tumor Necrosis Factor-alpha; D000514:alpha 1-Antichymotrypsin; D015847:Interleukin-4; D002097:C-Reactive Protein