Inhibition of IL-17A in atherosclerosis

Atherosclerosis. 2011 Apr;215(2):471-4. doi: 10.1016/j.atherosclerosis.2010.12.034. Epub 2011 Jan 19.

Abstract

Objective: To determine the effects of interleukin (IL)-17A inhibition on experimental atherosclerosis.

Methods and results: ApoE(-/-) mice were treated with either rat anti-mouse IL-17A, mouse anti-mouse IL-17A or isotype-matched control antibodies for 12 weeks (n=8-10 per group). Ldlr(-/-) mice were transplanted with IL-17A-deficient or wild type bone marrow (n=8 per group). Rat anti-mouse IL-17A treatment obviously reduced plaque size by 43% (p<0.01) without evidence of reduced IL-17A signaling. In contrast, mouse anti-mouse IL-17A treatment and IL-17A deficiency in bone marrow cells did not alter lesion size despite significant reduction of IL-17A production.

Conclusions: Inhibition of IL-17A signaling does not alter lesion development in Th1-biased C57BL/6 ApoE(-/-) and Ldlr(-/-) mice with already low levels of IL-17A production. Alteration of lesion development after repeated injections of rat anti-mouse IL-17A antibody in ApoE(-/-) mice could not be attributed to blockade of IL-17A signaling.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antibodies / pharmacology
  • Apolipoproteins E / deficiency
  • Atherosclerosis / immunology*
  • Atherosclerosis / prevention & control
  • Female
  • Interleukin-17 / antagonists & inhibitors*
  • Interleukin-17 / immunology
  • Interleukin-17 / physiology
  • Male
  • Mice
  • Mice, Inbred C57BL
  • Plaque, Atherosclerotic / prevention & control
  • Rats
  • Receptors, LDL / deficiency
  • Signal Transduction / drug effects

Substances

  • Antibodies
  • Apolipoproteins E
  • Interleukin-17
  • Receptors, LDL