Interleukin-4 suppression of monocyte tumour necrosis factor-alpha production. Dependence on protein synthesis but not on cyclic AMP production.
The molecular mechanisms by which human interleukin-4 (IL-4) down-regulates tumour necrosis factor-alpha (TNF-alpha) production by monocytes remain unknown. Other studies of IL-4 action in B lymphocytes and large granular lymphocytes (LGL) suggested that IL-4 may suppress mediator production by augmenting intracellular cyclic AMP (cAMP) levels. However, this study did not find evidence for involvement of a cAMP-dependent signalling pathway for expression of IL-4 activity in monocytes. IL-4 reduced TNF-alpha production by monocytes when IL-4 and lipopolysaccharide (LPS) were added concomitantly, or upon subsequent activation by LPS 16 hr after first exposure to IL-4. The continued presence of IL-4 at the time of LPS stimulation was not necessary; however, the suppressive effects of IL-4 were dependent on protein synthesis. This sustained activity of IL-4 for down-regulation of the production of inflammatory signals may be important for control in vivo of excessively activated monocytes/macrophages, and in therapy.
Hart
P H
PH
Department of Microbiology and Infectious Diseases, School of Medicine, Flinders University of South Australia, Aelaide.
Jones
C A
CA
Finlay-Jones
J J
JJ
D002478:Cells, Cultured; D000242:Cyclic AMP / Q000097:blood*; D006801:Humans; D015847:Interleukin-4 / Q000276:immunology*; D008070:Lipopolysaccharides / Q000276:immunology; D009000:Monocytes / Q000276:immunology*; D013997:Time Factors; D014409:Tumor Necrosis Factor-alpha / Q000096:biosynthesis*
D008070:Lipopolysaccharides; D014409:Tumor Necrosis Factor-alpha; D015847:Interleukin-4; D000242:Cyclic AMP