ANTI-CD18 MONOCLONAL-ANTIBODY SLOWS EXPERIMENTAL AORTIC-ANEURYSM EXPANSION

Purpose: Inflammation has been implicated as a contributing factor in the expansion of abdominal aortic aneurysms (AAA). To test this hypoth esis, we examined the effects of a monoclonal antibody (MAB) to the le ukocyte CD18 adhesion molecule on the expansion of experimental AAA. M ethods: Aneurysms were induced by perfusion of an isolated segment of the infrarenal aorta with elastase in 22 normotensive (WKY) and 17 gen etically hypertensive (WKHT) rats. Animals of both strains were random ly allocated to control or MAB-treated groups (MAB, 5 mu g/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 how cytometry . Aortic size was directly measured initially and on day 14. At that t ime, a segment of aorta was stained with hematoxylin and eosin and mon onuclear leukocytes and neutrophils were counted in each of 10 microsc opic fields (400 x). Results: The initial aortic size in all animals w as 1.11 +/- 0.15 mm. All groups developed aneurysms significantly larg er than the initial aortic size (p < 0.01). However, the MAB-treated a nimals had significantly smaller aneurysms than the untreated controls (mm): WKY: 3.63 +/- 1.26, WRY-MAB: 2.08 +/- 0.30, WKHT: 4.54 +/- 1.86 , WKHT-MAB: 2.37 +/- 0.40, p < 0.0001. There also were significantly f ewer 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 slow s the expansion of AAA in this experimental model. The associated infl ammatory process at day 14, as indicated by monocyte infiltration, is reduced, but this effect may be opposed by the presence of hypertensio n. Further evaluation of the role of leukocytes and adhesion molecules in the expansion of AAA is warranted.