lnterleukin-4 Differentially Regulates Tumor Necrosis Factor-α Gene Expression by Human T Lymphocytes and Monocytes

Abstract

Tumor necrosis factor-α (TNF-α), a product of both mononuclear phagocytes and T lymphocytes, is an important proximal mediator of a number of acute and chronic inflammatory disease states. In this investigation we examine the regulatory effects of the lymphocyte product interleukin-4 (IL-4) on the gene expression of TNF-α from stimulated human peripheral blood monocytes (PBM) and T lymphocytes. We demonstrated the dose-dependent suppression of TNF-α mRNA and protein synthesis from lipopolysaccharide-treated PBM by IL-4. The suppressive effects of IL-4 appear to be dependent upon de novo protein synthesis, as cycloheximide abrogated the IL-4-induced reduction in TNF-α mRNA levels from PBM. In contrast to the suppressive effects of IL-4 on PBM-derived cytokine expression, IL-4 did not alter TNF-α mRNA expression from α-Cd3 or PMA + α-CD-28-treated T lymphocytes. Moreover, IL-2 mRNA expression from similarly treated T lymphocytes was unaltered by IL-4. Our findings demonstrate that disparity exists in the regulation of TNF-α gene expression from different immune cell populations which may have important implications in the evolution of acute and chronic inflammatory responses.