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AIM To evaluate the immunomodulatory effect of oral administration of PRX-106 in the high-fat diet model.METHODS For 22 wk, C57BL/6 HFD-fed mice received daily oral treatments with BY-2 cells expressing recombinant antitumor necrosis factor alpha fusion protein(PRX-106). Mice were followed for serum liver enzyme and triglyceride levels, liver histology and intrahepatic and systemic FACS.RESULTS The orally administered non-absorbable PRX-106 w a s b i o l o g i c a l l y a c t i v e. A l t e r e d d i s t r i b u t i o n o f CD4+CD25+Fox P3+ between the liver and spleen and an increase in the intrasplenic-to-intrahepatic CD4+CD25+Fox P3+ ratio and a decrease in the intrasplenic-to-intrahepatic CD8+CD25+Fox P3+ ratio were observed. An increase in intrahepatic NKT cells and a decrease in the intrasplenic-to-intrahepatic NKT ratio were noted. Assessment of the CD4-to-CD8 ratios showed sequestration of CD8+ lymphocytes in the liver. These effects were associated with a decrease in serum triglyceride levels, decrease in the aspartate aminotransferase levels, serum glucose levels, and HOMA-IR score. A decrease in hepatic triglycerides content was observed in the high dose-treated mice.CONCLUSION Orally administered PRX-106 shows biological activity and exerts an immunomodulatory effect, alleviating liver damage. The data suggest that PRX-106 may provide an oral immunotherapy for nonalcoholic steatohepatitis.
AIM To evaluate the immunomodulatory effect of oral administration of PRX-106 in the high-fat diet model. METHODS For 22 wk, C57BL / 6 HFD-fed mice received daily oral treatments with BY-2 cells expressing recombinant antitumor necrosis factor alpha fusion protein (PRX-106). Mice were followed for serum liver enzyme and triglyceride levels, liver histology and intrahepatic and systemic FACS .RESULTS The orally administered non-absorbable PRX-106 wasbiologically activated e. A ltereddistributionof CD4 + CD25 + Fox P3 + between the liver and spleen and an increase in the intrasplenic-to-intrahepatic CD4 + CD25 + Fox P3 + ratio and a decrease in the intrasplenic-to-intrahepatic CD8 + CD25 + Fox P3 + ratio were observed. An increase in intrahepatic NKT cells and a decrease in the intrasplenic -to-intrahepatic NKT ratio were noted. Assessment of CD4-to-CD8 ratios showed sequestration of CD8 + lymphocytes in the liver. These effects were associated with a decrease in serum tri glycerin levels, decreased in the aspartate aminotransferase levels, serum glucose levels, and HOMA-IR score. A decrease in hepatic triglycerides content was observed in the high dose-treated mice. The data suggest that PRX-106 may provide an oral immunotherapy for nonalcoholic steatohepatitis.