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.

[1]  C. Sturgeon,et al.  Acute‐phase protein response, survival and tumour recurrence in patients with colorectal cancer , 2001, The British journal of surgery.

[2]  I. Kushner,et al.  Acute-phase proteins and other systemic responses to inflammation. , 1999, The New England journal of medicine.

[3]  H. R. Chang,et al.  Role of cytokines in AIDS wasting , 1998, Nutrition.

[4]  C. Grunfeld.  The wasting syndrome in AIDS: mechanisms and implications. , 1998, Nutrition.

[5]  K. Fearon,et al.  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 , 1998 .

[6]  D. McMillan,et al.  Albumin synthesis rates are not decreased in hypoalbuminemic cachectic cancer patients with an ongoing acute-phase protein response. , 1998, Annals of surgery.

[7]  K. Fearon,et al.  Contribution of anorexia and hypermetabolism to weight loss in anicteric patients with pancreatic cancer , 1997, The British journal of surgery.

[8]  E. Wouters,et al.  Evidence for a relation between metabolic derangements and increased levels of inflammatory mediators in a subgroup of patients with chronic obstructive pulmonary disease. , 1996, Thorax.

[9]  S. Heys,et al.  Modulation of the cytokine and acute‐phase response to major surgery by recombinant interleukin 2 , 1995, The British journal of surgery.

[10]  G. Ramsay,et al.  Natural cytokine antagonists and endogenous antiendotoxin core antibodies in sepsis syndrome. The Sepsis Intervention Group. , 1995, JAMA.

[11]  J. Ross,et al.  Acute‐phase protein response and survival duration of patients with pancreatic cancer , 1995, Cancer.

[12]  F. Schildberg,et al.  Downregulation of proinflammatory cytokine release in whole blood from septic patients. , 1995, Blood.

[13]  J. Kehayias,et al.  Rheumatoid cachexia: cytokine-driven hypermetabolism accompanying reduced body cell mass in chronic inflammation. , 1994, The Journal of clinical investigation.

[14]  J. Ross,et al.  Cytokines, the Acute‐Phase Response, and Resting Energy Expenditure in Cachectic Patients with Pancreatic Cancer , 1994, Annals of surgery.

[15]  W. Simpson,et al.  Correlation of serum cytokine and acute phase reactant levels with alterations in weight and serum albumin in patients receiving immunotherapy with recombinant IL‐2 , 1994, Clinical and experimental immunology.

[16]  T. Mosmann,et al.  IL-10 inhibits cytokine production by activated macrophages. , 1991, Journal of immunology.

[17]  C. Figdor,et al.  Interleukin-4 (IL-4) inhibits secretion of IL-1 beta, tumor necrosis factor alpha, and IL-6 by human monocytes. , 1990, Blood.

[18]  S. Swisher,et al.  Interleukin‐4 Downregulates Interleukin‐6 Production in Human Peripheral Blood Mononuclear Cells , 1990, Journal of leukocyte biology.

[19]  J V Castell,et al.  Interleukin-6 and the acute phase response. , 1990, The Biochemical journal.

[20]  D. Morton,et al.  IL-4 down-regulates IL-1 and TNF gene expression in human monocytes. , 1989, Journal of immunology.

[21]  C. Figdor,et al.  Modulation of phenotypic and functional properties of human peripheral blood monocytes by IL-4. , 1988, Journal of immunology.