EVIDENCE THAT EOSINOPHIL INFILTRATION IN THE OK-432 FIBRINOGEN-INJECTED METH-A TUMOR IN MICE IS MEDIATED BY LOCALLY PRODUCED IL-5/

It was previously demonstrated that a single injection of OK-432 (a pe nicillin-treated freeze-dried Streptococcus) mixed with fibrinogen int o cancer tissues induces marked infiltration by eosinophils of the tum or stroma and leads to tumor necrosis. In the present study, we examin ed mechanisms regulating the local accumulation of eosinophils and the role of infiltrating eosinophils in tumor regression using the OK-432 /fibrinogen injected Meth-A fibrosarcoma tumor. After injection of OK- 432/fibrinogen into the tumor on the left flank of the BALB/c mice, eo sinophil infiltration became obvious in the tumor stroma on day 3 foll owing the accumulation of macrophages and neutrophils, was massive on day 5 and decreased by day 10. After the decrease in the infiltration of eosinophils, the tumor injected with OK-432/fibrinogen diminished m arkedly in size with ulceration as compared with control. Northern blo t analysis revealed that expression of IL-5 mRNA in the tumor tissue w as not detected on day 0, was significantly on day 3, reached the maxi mum on day 5, and thereafter decreased by day 10. Although intraperito neal injection of rat anti-IL-5 monoclonal antibody in tumor bearing m ice prior to OK-432 injection inhibited the infiltration of eosinophil s, the antitumor effects of OK-432 persisted. In the blood, neither eo sinophilia nor IL-5 activity was recognized during the course of the e xperiment. These results suggest that intratumoral injection of OK-432 /fibrinogen induces local production of IL-5, which in turn recruits e osinophils into the tumor tissue, however, the infiltrating eosinophil s do not play an important role in tumor regression. (C) 1998 Internat ional Society for Immunopharmacology.