title: Anti-CD 18 monoclonal antibody slows experimental aortic aneurysm expansion.
abstract: OBJECTIVE
  Inflammation has been implicated as a contributing factor in the expansion of abdominal aortic aneurysms (AAA). To test this hypothesis, we examined the effects of a monoclonal antibody (MAB) to the leukocyte CD18 adhesion molecule on the expansion of experimental AAA.
  
  
  METHODS
  Aneurysms were induced by perfusion of an isolated segment of the infrarenal aorta with elastase in 22 normotensive (WKY) and 17 genetically hypertensive (WKHT) rats. Animals of both strains were randomly allocated to control or MAB-treated groups (MAB, 5 microgram/100 gm body weight intraperitoneally, daily, beginning on the operative day for a total of four doses). The activity of the MAB against rat leukocytes had first been determined by in vitro immunofluorescence flow cytometry. Aortic size was directly measured initially and on day 14. At that time, a segment of aorta was stained with hematoxylin and eosin and mononuclear leukocytes and neutrophils were counted in each of 10 microscopic fields (400X).
  
  
  RESULTS
  The initial aortic size in all animals was 1.11+/-0.15 mm. All groups developed aneurysms significantly larger than the initial aortic size (p<0.01). However, the MAB-treated animals had significantly smaller aneurysms than the untreated controls (mm): WKY: 3.63+/-1.26, WKY-MAB: 2.08+/-0.30, WKHT: 4.54+/-1.86, WKHT-MAB: 2.37+/-0.40, p<0.0001. There also were significantly fewer monocytes in the MAB-treated normotensive rats: WKY:35.5+/-29.9, WKHT:40.6+/-28.8, WKY-MAB: 8.9+/-8.5, WKHT-MAB: 32.3+/-25.7, p=0.03. Neutrophil counts did not differ significantly between the groups.
  
  
  CONCLUSIONS
  Treatment with anti-CD18 monoclonal antibody slows the expansion of AAA in this experimental model. The associated inflammatory process at day 14, as indicated by monocyte infiltration, is reduced, but this effect may be opposed by the presence of hypertension. Further evaluation of the role of leukocytes and adhesion molecules in the expansion of AAA is warranted.
authors.affiliation: Department of Surgery, The University of Vermont College of Medicine, Burlington, Vermont, USA.
authors.forename: M A
authors.initials: MA
authors.lastname: Ricci
authors.forename: G
authors.initials: G
authors.lastname: Strindberg
authors.forename: J M
authors.initials: JM
authors.lastname: Slaiby
authors.forename: R
authors.initials: R
authors.lastname: Guibord
authors.forename: L J
authors.initials: LJ
authors.lastname: Bergersen
authors.forename: P
authors.initials: P
authors.lastname: Nichols
authors.forename: E D
authors.initials: ED
authors.lastname: Hendley
authors.forename: D B
authors.initials: DB
authors.lastname: Pilcher
mesh_terms: D000818:Animals; D000911:Antibodies, Monoclonal / Q000276:immunology / Q000627:therapeutic use*; D001012:Aorta, Abdominal / Q000276:immunology / Q000473:pathology; D017544:Aortic Aneurysm, Abdominal / Q000276:immunology / Q000473:pathology / Q000517:prevention & control*; D018821:CD18 Antigens / Q000276:immunology*; D004195:Disease Models, Animal; D018450:Disease Progression; D005434:Flow Cytometry; D007274:Injections, Intraperitoneal; D007958:Leukocyte Count; D007962:Leukocytes / Q000276:immunology; D007963:Leukocytes, Mononuclear / Q000276:immunology; D009504:Neutrophils / Q000276:immunology; D010196:Pancreatic Elastase / Q000009:adverse effects; D051381:Rats; D011918:Rats, Inbred SHR; D011921:Rats, Inbred WKY
chemical_list: D000911:Antibodies, Monoclonal; D018821:CD18 Antigens; D010196:Pancreatic Elastase