The effects of intravenous immunoglobulin on intestinal inflammation: a systematic review of animal and clinical studies.

Background: Intestinal inflammation encompasses a range of conditions, including inflammatory bowel disease (IBD), radiation-induced enteritis, and chemotherapy- or toxin-induced epithelial injury. Although intravenous immunoglobulin (IVIg) is widely used in autoimmune and inflammatory disorders, its role in these forms of intestinal injury has not been systematically evaluated. Objective: This systematic review aimed to summarize the existing animal and clinical evidence on the therapeutic effects of IVIg in intestinal inflammation. Methods: This systematic review was conducted in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) 2020 guidelines. Four electronic databases (PubMed, Web of Science, Embase, and China National Knowledge Infrastructure) were systematically searched for studies published from January 1, 2000 to February 3, 2026. Eligible studies included animal and clinical investigations evaluating the role of IVIg in the context of intestinal inflammation. Data were narratively synthesized, and risk of bias was assessed using the SYstematic Review Centre for Laboratory animal Experimentation (SYRCLE) tool for animal studies and Risk Of Bias In Non-randomized Studies - of Interventions (ROBINS-I) for non-randomized clinical studies. Results: Ten studies were included: seven animal and three clinical studies. IVIg generally exhibited anti-inflammatory and epithelial-protective effects across models of Dextran Sulfate Sodium (DSS)-induced colitis, radiation-induced enteritis, chemotherapy-induced mucositis, and toxin-induced epithelial damage. Reported mechanisms included interleukin (IL)-10 signaling, Fcγ receptor modulation, ferroptosis inhibition, and microbiota-mediated immune regulation. Human data were restricted to small, retrospective, uncontrolled cohorts of patients with refractory or steroid-resistant IBD, often with contraindications to standard immunosuppressive therapy. In these studies, some patients experienced short-term clinical improvement, but responses were variable, long-term outcomes were frequently unsatisfactory, and the overall risk of bias was serious to critical. Conclusion: Current animal and clinical data suggest that IVIg can modulate intestinal inflammation and epithelial injury but are insufficient to support its use as a standard therapy for IBD or other intestinal inflammatory conditions. At present, IVIg should be considered, at most, as an adjunctive or rescue option in carefully selected, refractory cases in which guideline-recommended therapies are ineffective or contraindicated. Further work is needed to improve the rigour and transparency of preclinical studies and to conduct small, well-designed prospective clinical studies in clearly defined niche indications to clarify any potential role of IVIg within the expanding therapeutic armamentarium for intestinal inflammation. PROSPERO ID (CRD420251051592).