Selective regulation of intercellular adhesion molecule‐1 expression by interleukin‐18 and interleukin‐12 on human monocytes

Abstract

SummaryInduction of expression of adhesion molecules is a crucial step in inflammation. The role of interleukin‐18 (IL‐18) in induction of various adhesion molecules was investigated in freshly isolated peripheral blood mononuclear cells and human monocyte and T‐cell lines. IL‐18 selectively up‐regulated intercellular adhesion molecule‐1 (ICAM‐1) expression on freshly isolated human monocytes, but not on lymphocytes. The expression of other adhesion molecules was not influenced. Induction of ICAM‐1 by IL‐18 was dependent on endogenous tumour necrosis factor‐α (TNF‐α), and IL‐12 had an additive effect on that of IL‐18. No changes in adhesion molecule expression were observed on the monocytic cell line THP‐1 and on the T‐cell lines HSB‐2 and Jurkat J16. In addition, induction of ICAM‐1 on monocytes by lipopolysaccharide was slightly, but significantly, inhibited by blockade of either endogenous IL‐18 or TNF‐α with IL‐18 binding protein or TNF binding protein, respectively. Blocking IL‐1 effects with IL‐1 receptor antagonist did not influence ICAM‐1 levels. In conclusion, IL‐18 selectively up‐regulates the expression of ICAM‐1 on monocytes, and this contributes to the proinflammatory effects of this cytokine.