Interleukin-4 suppression of monocyte tumour necrosis factor-α 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-α (TNF-α) 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-α 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.