Improvement of Macrophage Dysfunction by Administration of Anti‐transforming Growth Factor‐β Antibody in EL4‐bearing Hosts

An experimental therapy for improvement of macrophage dysfunction caused by transforming growth factor-β (TGF-β) was tried in EL4 tumor-bearing mice. TGF-β was detected in cell-free ascitic fluid from EL4-bearers, but not in tbat from normal mice, by western blot analysis. The ascites also showed growth-suppressive activity against MvlLn cells, and the suppressive activity was potentiated by transient acidification. To investigate whether the functions of peritoneal macrophagcs were suppressed in EL4-bearers, the abilities to produce nitric oxide and tumor necrosis factor-α (TNF-α) upon lipopolysaccharide (LPS) stimulation were measured. Both abilities of macrophages in EL4-bearing mice were suppressed remarkably on day 9, and decreased further by day 14, compared with non-tumor-bearing controls. TGF-β activity was abrogated by administration of anti-TGF-α antibody to EL4-bearing mice. While a large amount of TGF-β was detected in ascitic fluid from control EL4-bearers, little TGF-β was detectable in ascites from EL4-bearers given anti-TGF-β antibody. Furthermore, while control macrophages exhibited little or no production of nitric oxide and TNF-α on LPS stimulation in vitro, macrophages from EL4-bearers administered with anti-TGF-β antibody showed the same ability as normal macrophages. These results clearly indicate that TGF-β contributes to macrophage dysfunction and that the administration of specific antibody for TGF-β reverses macrophage dysfunction in EL4-bearing hosts.