The magnitude of the immune response to heat shock protein-65 following BCG immunisation is associated with the extent of experimental atherosclerosis.

Several studies have reported associations between coronary heart disease (CHD) and infection. Recent studies have implicated immune responses to heat shock protein(s) (HSP) as a contributary factor. Using an immunisation model, we have assessed the relationship between the immune responses to HSP and subsequent atherosclerosis. Rabbits were immunised with bacillus Calmette-Guerin (BCG) vaccine (n=10) or saline (n=10) and subsequently fed a 0.25-1.0% cholesterol diet for 10 weeks. Plasma levels of IgG specific for mycobacterial antigen A60 and human HSP-60, but not for human HSP-70, rose following BCG immunisation, reaching a peak after 8 weeks. The percentage aortic area covered by atherosclerotic plaque was greater in animals immunised with BCG (30.5+/-3.8) compared to saline treated animals (16.4+/-2.6) (P<0.05). Furthermore, the individual titres of anti-HSP-60 in the BCG-immunised animal antibodies at week 8 (prior to starting the cholesterol diet) correlated with the percentage aortic area covered by plaque after 18 weeks (R2=0.72; P<0.05). No correlation was found between anti-A60 antibody titres and plaque area. Antiserum from BCG-immunised, but not control, animals stained heat-shocked endothelial cells. These data suggest that immune responses to HSP may be implicated in the relationship between specific infections and CHD.