Abstracts
2002 Digestive Disease Week

# 105714 Abstract ID: 105714 Intravenous Immunoglobulin (IVIG) Protects against the Devlopment of Systemic Injury Following Mesenteric Ischemia Reperfusion
Jimie Anderson, Sherry Fleming, George Tsokos, Christopher Swiecki, Terez Shea-Donohue, Washington, DC; Silver Spring, MD; Beltsville, MD

Background: Mesenteric ischemia-reperfusion (IR) injury and inflammation are considered critical for activation and release of inflammatory mediators that cause distant organ dysfunction. Pulmonary macromolecular leak after IR is linked to elevated neutrophil number, activity and adhesion molecule expression. Previously, we showed that IR-induced mucosal injury was maximal at 2 hrs, while systemic injury developed at 4 hrs into the reperfusion period. IVIG is an immunomodulator with beneficial effects associated with inhibition of complement-mediated tissue damage by scavenging active C3, preventing deposition into tissue. Aim: To determine the ability of IVIG to protect against the development of systemic injury after mesenteric IR. Methods: Male rats received infusions (total volume 1-1.5ml) of vehicle or IVIG (600mg/kg) over 15 min, 5 min before sham operation (SHAM) or 30 min of superior mesenteric artery occlusion followed by 4 hrs of reperfusion. Tissue PMN infiltration and serum PMN number were measured. Changes in lung capillary permeability were assessed by giving Evans blue dye was given 1 hour before euthanasia. Values were expressed as dye concentrations in bronchoalveolar lavages (BAL)/serum. PMN oxidative burst and CD18 expression were analyzed by flow cytometry. C3 and IgG deposition in sections (5 µ) of small intestine and lung were evaluated by immunohistochemistry. Results: IR increased mucosal injury (decreased villus height, VH), PMN infiltration, systemic PMN number, oxidative burst and CD18 expression. IVIG alone was associated with increased CD18 expression, but attenuated IR-induced changes in systemic PMN number, oxidative burst, and CD18 expression without reducing neutrophil infiltration. IVIG also inhibited IR-induced pulmonary leak. In IR VEH, the intense staining of both IgG and C3 in intestinal lamina propria and lung interstitium was reduced by IVIG to SHAM levels. Conclusion: IVIG protected against local mucosal injury and subsequent pulmonary macromolecular leak in rats despite increased tissue PMN infiltration. The decreased lung capillary leak shows that IVIG attenuates distant, as well as local, organ injury. Thus, IVIG may be a beneficial therapeutic intervention in systemic inflammatory response and multiple organ dysfunction.