Prevention of experimental myointimal hyperplasia by immunomodulation.
BACKGROUND
we have tested the hypothesis that treatment with a mycobacterial preparation that modulates the antibody response, would diminish restenosis in a rat angioplasty model.


METHODS
male Sprague-Dawley rats were used. All immunisations were given subcutaneously. Group A (control) received normal saline on days 0, 21, and 42. Group B received SRL172 on days 0, 21, and 42. Group C received SRL172 on days 0, 21, and 42, and hsp65/Incomplete Freund's on days 21 and 42. Group D received hsp65/Freund's on days 21 and 42. Right common carotid arteries were balloon-injured on day 63 using a standard technique known to produce MIH and animals were sacrificed on day 77. For each carotid 6 microm cross sections were cut from paraffin blocks. Cross-sectional areas were measured by computerised planimetry.


RESULTS
balloon injury resulted in MIH in all animals. Data represents mean+/-SEM for the percentage of area enclosed within the internal elastic lamina occupied by MIH (% MIH); which for groups A, B, C, and D was 85+/-11, 24+/-3, 27+/-7, and 17+/-3 respectively. All the treatment groups had significantly less MIH when compared to the control group but no statistically significant difference was found between any of the treatment groups.


CONCLUSIONS
this is the first report that immunomodulation with mycobacterial material suitable for use in man, can reduce MIH. Since such modulation has low risk, this raises the prospect of an important new therapeutic modality to combat restenosis.
Stansby
G
G
Academic Surgical Unit, Imperial College School of Medicine at St. Mary's, London, UK.
Chan
Y C
YC
Berwanger
C S
CS
Shurey
S
S
Rook
G A W
GA
Stanford
J L
JL
D000276:Adjuvants, Immunologic / Q000627:therapeutic use*; D000800:Angioplasty, Balloon; D000818:Animals; D000942:Antigens, Bacterial / Q000276:immunology; D001426:Bacterial Proteins; D001428:Bacterial Vaccines / Q000627:therapeutic use*; D020212:Carotid Artery Injuries; D017536:Carotid Artery, Common / Q000473:pathology*; D016893:Carotid Stenosis / Q000473:pathology / Q000517:prevention & control* / Q000628:therapy; D018834:Chaperonin 60; D018833:Chaperonins / Q000276:immunology; D003251:Constriction, Pathologic; D006965:Hyperplasia; D008297:Male; D009131:Muscle, Smooth, Vascular / Q000473:pathology*; D009161:Mycobacterium / Q000276:immunology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D012008:Recurrence; D017539:Tunica Intima / Q000473:pathology*; D015164:Vaccines, Inactivated / Q000627:therapeutic use
D000276:Adjuvants, Immunologic; D000942:Antigens, Bacterial; D001426:Bacterial Proteins; D001428:Bacterial Vaccines; D018834:Chaperonin 60; D015164:Vaccines, Inactivated; C074119:heat-shock protein 65, Mycobacterium; D018833:Chaperonins