Preventive effects of <i>hochuekkito</i>, a traditional <scp>Japanese</scp> herbal formula comprising <i><scp>Atractylodis</scp> rhizoma</i>, on anti‐<scp>PD</scp>‐1 antibody‐induced intestinal mucositis through the elimination of self‐reactive <scp>

Abstract Aim This study aimed to create a mouse model of adverse drug reactions and examine the effect of hochuekkito composed of Atractylodis rhizoma (AtR‐ hochuekkito ) and thought to improve the elimination of autoreactive T lymphocytes in Peyer's patches. Methods We investigated whether an antibody cocktail consisting of an anti‐mouse PD‐1 antibody as a sham immune checkpoint inhibitor and anti‐mouse CD3 antibodies induced small‐intestinal mucosal inflammation and lung inflammation. Then we analyzed AtR‐ hochuekkito 's effects on small‐intestinal mucosal inflammation induced by the antibody cocktail. Results The antibody cocktail aggravated small‐intestinal mucosal inflammation and lung inflammation induced by anti‐CD3 antibody alone. Pretreatment with AtR‐ hochuekkito prevented small‐intestinal mucosal inflammation induced by the antibody cocktail. One month of pretreatment with AtR‐ hochuekkito may induce an influx of inactive regulatory CD8‐positive T cells into the small‐intestinal tissue and eliminate autoreactive T cells by increasing autoimmune regulators in Peyer's patches. Conclusion AtR‐ hochuekkito was suggested to prevent small‐intestinal inflammation induced by an antibody cocktail. AtR‐ hochuekkito , when started prophylactically before administration of immune checkpoint inhibitors, may prevent the development of adverse effects caused by immune checkpoint inhibitors and may contribute to the completion of cancer treatment with immune checkpoint inhibitors.