Interleukin-4 does not influence development of hypercholesterolemia or angiotensin II-induced atherosclerotic lesions in mice.
Interleukin-4 (IL-4) has been detected in both human and mouse atherosclerotic lesions, although its effects on the development of the disease are undefined. We determined the role of IL-4 in the most commonly used murine models of atherosclerosis by defining the effects of exogenous delivery and genetic deficiency of this cytokine on both hypercholesterolemia and AngII-induced atherosclerosis in apolipoprotein E (apoE)(-/-) mice and different dietary stimuli in low-density lipoprotein (LDL) receptor(-/-) mice. Exogenous administration of IL-4 (1.1 ng g(-1) day(-1) i.p. for 30 days) into female apoE(-/-) mice had no effect on lesion size or composition in mice fed normal or saturated fat diets. Also, IL-4 deficiency had no significant effect on the size or composition of atherosclerotic lesions in two vascular areas of male and female apoE(-/-) mice fed either a normal or saturated fat diet. IL-4 deficiency was also studied in age-matched male mice infused with AngII (1000 ng kg(-1) min(-1)) for 28 days. Whereas AngII infusion augmented atherosclerotic lesion formation, IL-4 deficiency did not influence atherosclerotic lesion size or composition. Finally, different dietary stimuli also had no effect on atherosclerotic lesion size in female LDL receptor(-/-) mice. These data demonstrate that IL-4 does not significantly influence the development of atherosclerotic lesions in apoE(-/-) mice of either gender or in female LDL receptor(-/-) mice, irrespective of the mode of induction of atherosclerosis.
Cardiovascular Research Center, Wethington Building, Room 562, University of Kentucky, Lexington, KY 40536-0200, USA. vicky.king@uky.edu
Victoria L
VL
King
Lisa A
LA
Cassis
Alan
A
Daugherty
D000804:Angiotensin II / Q000008:administration & dosage / Q000633:toxicity; D000818:Animals; D001057:Apolipoproteins E / Q000235:genetics; D050197:Atherosclerosis / Q000139:chemically induced / Q000378:metabolism* / Q000473:pathology*; D004195:Disease Models, Animal; D005260:Female; D006937:Hypercholesterolemia / Q000378:metabolism*; D015847:Interleukin-4 / Q000378:metabolism* / Q000494:pharmacology; D008297:Male; D051379:Mice; D008817:Mice, Mutant Strains; D011973:Receptors, LDL / Q000235:genetics
D001057:Apolipoproteins E; D011973:Receptors, LDL; D000804:Angiotensin II; D015847:Interleukin-4