DIFFERENTIAL-EFFECTS OF INTERLEUKIN-1 RECEPTOR ANTAGONIST AND TUMOR-NECROSIS-FACTOR BINDING-PROTEIN ON FATTY-STREAK FORMATION IN APOLIPOPROTEIN E-DEFICIENT MICE

Background-The cytokines interleukin 1 (IL-1) and tumor necrosis facto r (TNF) are secreted by the different cell populations of the vascular wall and have been suggested to promote atherosclerosis, Methods and Results-Their respective roles in fatty-streak formation in apolipopro tein E-deficient mice were investigated by use of IL-1 receptor antago nist and TNF binding protein. Estradiol-17 beta was used as a positive control. Blocking TNF seemed to be active in female animals but not i n males. IL-1 receptor antagonist was as effective as or more effectiv e than estradiol in both sexes. Conclusions-IL-1 plays a crucial role in the initial step of the atherosclerotic process in this animal mode l, and blocking the activity of this cytokine should be considered as a therapeutic possibility.