INTERLEUKIN-4 PREVENTS THE INDUCTION OF TISSUE FACTOR MESSENGER-RNA IN HUMAN MONOCYTES IN RESPONSE TO LPS OR PMA STIMULATION

Increased expression of tissue factor (TF) procoagulant activity by bl ood monocytes and tissue macrophages is implicated in a number of thro mbotic disorders, as well as in fibrin deposition associated with infl ammatory lesions and immunological diseases. We found that interleukin 4 (IL-4), a T lymphocyte-derived cytokine known to regulate a number of monocyte functions, inhibited the production of TF by monocytes in response to endotoxin and phorbol myristate acetate (PMA) in vitro. IL -4 had a concentration-dependent inhibitory effect on functional TF pr ocoagulant activity (PCA) and reduced the binding of an anti-TF antibo dy, as assessed by flow cytometry analysis. Moreover, IL-4 reduced LPS - and PMA-induced TF mRNA levels. TF mRNA stability was not modified b y IL-4 after the arrest of transcription by actinomycin D. We thus con clude that mRNA suppression is mediated by an effect occurring at the transcriptional level. Our results also show that the suppressive effe ct of IL-4 is independent of an increase in the intracellular concentr ation of cyclic AMP, another established inhibitor of TF production. L ocally produced IL-4 might thus contribute to limiting the consequence s of monocyte activation.