Mucositis is a major clinical complication associated with
cancer treatment and may limit the benefit of
chemotherapy. Leukocytes and inflammatory mediators have been extensively associated with
mucositis severity. However, the role of eosinophils in the pathophysiology of
chemotherapy-induced
mucositis remains to be elucidated. Here, using GATA-1-deficient mice, we investigated the role of eosinophils in intestinal
mucositis. There was marked accumulation of eosinophils in mice given
irinotecan and eosinophil ablation inhibited intestinal
mucositis. Treatment with Evasin-4, a
chemokine receptor antagonist, reduced the recruitment of eosinophils and decreased
irinotecan-induced
mucositis. Importantly, Evasin-4 did not interfere negatively with the antitumour effects of
irinotecan. Evasin-4 was of benefit for mice given high doses of
irinotecan once Evasin-4-treated mice presented delayed mortality. Altogether, our findings suggest that Evasin-4 may have significant mucosal-protective effects in the context of
antineoplastic chemotherapy and may, therefore, be useful in combination with anticancer treatment in
cancer patients.