Serum-derived bovine immunoglobulin in the alleviation of irinotecan-induced mucositis.

Abstract

166 Background: Gastrointestinal (GI) mucositis is associated with diarrhoea and intestinal barrier dysfunction caused by apoptosis, immune dysfunction, and microbiome alterations. Serum-derived bovine immunoglobulin (SBI) has been shown to ameliorate inflammation in colitis models, has been shown to improve HIV-induced enteropathy and nutritional status, and is being investigated in post-surgical recovery in oncology patients. We investigated in a rat model whether SBI was effective in alleviating symptoms of GI mucositis. Methods: Animals were gavaged with 250 or 500mg/kg of SBI twice daily, before intraperitoneal administration of 200mg/kg irinotecan on day 4, and for 6 days post-irinotecan. Animals were monitored for bodyweight and diarrhoea. Tissues were collected at necropsy 6, 48, 96 and 144 hours post-irinotecan. H&E-stained colon and jejunum were analysed for histological damage. Results: The overall incidence, severity and duration of diarrhoea, and clinical symptoms of mucositis, were decreased in irinotecan-treated animals that had received SBI. Animals receiving 500 mg SBI/kg also tended to lose less bodyweight than animals treated only with irinotecan (P>0.10). Animals receiving SBI had less pronounced irinotecan-induced changes in neutrophil levels (P≈0.02), and lower tissue damage scores than those receiving irinotecan alone (P<0.0001). Conclusions: Twice-daily oral gavage of SBI was well-tolerated, and reduced the incidence, severity and duration of irinotecan-induced mucositis. SBI was associated with less pronounced changes in inflammatory cell levels and intestinal tissue damage. Ongoing experiments aim to explore the mechanisms of SBI-associated gastrointestinal protection.