INTERLEUKIN 4 INDUCES INTERLEUKIN 6 PRODUCTION BY ENDOTHELIAL-CELLS - SYNERGY WITH INTERFERON-GAMMA

Interleukin (IL) 4 induces IL 6 production by human umbilical vein endothelial cells (HUVEC) in a dose-dependent manner, as shown by bioassay and immunoprecipitation. Interferon (IFN)-gamma, which antagonizes IL 4 effects on leukocytes, synergized with IL 4 in the induction of IL 6 production by HUVEC. Contamination with endotoxin was excluded by heat-inactivated IL 4, preincubating with anti-IL 4 polyclonal antibody and the use of polymyxin B. The presence of IL 4 receptors on HUVEC was shown by affinity cross-linking with I-125-IL 4, revealing a 110-kDA binding protein. However, compared with the amount on T cells the 60 - 70-kDa cross-linked doublet was present at much lower levels. Additional lower molecular weight cross-linked proteins were isolated only with HUVEC, but the origin of these is unclear. IL 6 is a pluripotent cytokine produced by many cells which promotes the differentiation and growth of lymphocytes and the production of acute phase protein by hepatocytes, and is important in the regulation of immunity at systemic and local levels. Since IL 4 and IFN-gamma are produced by T cells, which are frequently associated with vascular endothelium during chronic inflammation, IL 4 is likely to be an important cytokine in the regulation of IL 6 and perhaps other cytokine production by endothelium in vivo.