Requisite role for interleukin-4 in the acceleration of fatty streaks induced by heat shock protein 65 or Mycobacterium tuberculosis

Atherosclerotic lesions can be induced in rabbits and mice immunized with h eat shock protein 65 (HSP65), In the current study, we investigated the rol e of interleukin (IL)-4 in the HSP65- and Mycobacterium tuberculosis (MT)-i nduced models that exhibit an inflammatory phenotype, Fatty streak formatio n in IL-4-knockout (IL-4 KO) mice immunized with WSP65 or MT was significan tly 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 studie d comparatively the extent of humoral and cellular immune responses to HSP6 5 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 i n the knockout mice, the pattern of secreting cytokines interferon-gamma an d IL-IO 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 proather ogenic in vivo) as compared with their wild-type controls. 12-/15-Lipoxygen ase expression, known to be regulated by IL-4 and to contribute to murine a therosclerosis, in the lesions was not influenced by the immunization proto col used or by IL-4 disruption. Thus, IL-4 may prove a principal cytokine i n the progression of early "inflammatory" atherosclerotic lesions and may s erve as a target for immunomodulation.