title: Requisite role for interleukin-4 in the acceleration of fatty streaks induced by heat shock protein 65 or Mycobacterium tuberculosis.
abstract: Atherosclerotic lesions can be induced in rabbits and mice immunized with heat shock protein 65 (HSP65). In the current study, we investigated the role of interleukin (IL)-4 in the HSP65- and Mycobacterium tuberculosis (MT)-induced models that exhibit an inflammatory phenotype. Fatty streak formation in IL-4-knockout (IL-4 KO) mice immunized with HSP65 or MT was significantly reduced when compared with lesions in wild-type C57BL/6 mice. However, when injected with control (HSP-free) adjuvant, no differences were evident in the lesion size between wild-type and the IL-4 KO mice. Next, we studied comparatively the extent of humoral and cellular immune responses to HSP65 in the IL-4 KO and wild-type mice, as those are thought to be influential in murine atherosclerosis. Anti-HSP65 antibody levels were reduced in the HSP65-immunized IL-4 KO mice as compared with their wild-type littermates, whereas no differences were evident between the groups with respect to the primary cellular immune response to HSP65. Other than the absence of IL-4 in the knockout mice, the pattern of secreting cytokines interferon-gamma and IL-10 in concanavalin A-primed splenocytes was similar between the groups. HSP65-primed inguinal lymphocytes from IL-4 KO mice immunized with HSP65 secreted higher levels of interferon-gamma (previously shown to be proatherogenic in vivo) as compared with their wild-type controls. 12-/15-Lipoxygenase expression, known to be regulated by IL-4 and to contribute to murine atherosclerosis, in the lesions was not influenced by the immunization protocol used or by IL-4 disruption. Thus, IL-4 may prove a principal cytokine in the progression of early "inflammatory" atherosclerotic lesions and may serve as a target for immunomodulation.
authors.affiliation: Research Unit of Autoimmune Diseases, Sheba Medical Center, Tel Hashomer, Israel.
authors.forename: J
authors.initials: J
authors.lastname: George
authors.forename: Y
authors.initials: Y
authors.lastname: Shoenfeld
authors.forename: B
authors.initials: B
authors.lastname: Gilburd
authors.forename: A
authors.initials: A
authors.lastname: Afek
authors.forename: A
authors.initials: A
authors.lastname: Shaish
authors.forename: D
authors.initials: D
authors.lastname: Harats
mesh_terms: D000818:Animals; D000906:Antibodies / Q000032:analysis; D001092:Arachidonate 12-Lipoxygenase / Q000378:metabolism; D001093:Arachidonate 15-Lipoxygenase / Q000378:metabolism; D001161:Arteriosclerosis / Q000097:blood / Q000276:immunology*; D001426:Bacterial Proteins; D002455:Cell Division; D018834:Chaperonin 60; D018833:Chaperonins / Q000276:immunology / Q000502:physiology*; D002784:Cholesterol / Q000097:blood; D005260:Female; D007114:Immunization; D007371:Interferon-gamma / Q000096:biosynthesis; D016753:Interleukin-10 / Q000096:biosynthesis; D015847:Interleukin-4 / Q000096:biosynthesis / Q000172:deficiency / Q000235:genetics / Q000502:physiology*; D008214:Lymphocytes / Q000473:pathology; D017737:Macrophages, Peritoneal / Q000201:enzymology; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout / Q000235:genetics; D009169:Mycobacterium tuberculosis / Q000276:immunology*; D012016:Reference Values
chemical_list: D000906:Antibodies; D001426:Bacterial Proteins; D018834:Chaperonin 60; C074119:heat-shock protein 65, Mycobacterium; D016753:Interleukin-10; D015847:Interleukin-4; D007371:Interferon-gamma; D002784:Cholesterol; D001092:Arachidonate 12-Lipoxygenase; D001093:Arachidonate 15-Lipoxygenase; D018833:Chaperonins