Somatostatin and octreotide modulate the function of Kupffer cells in liver cirrhosis

In our previous studies we have shown that somatostatin and octreotide modulate the function of peritoneal macrophages and Kupffer cells in noncirrhotic livers. However, the effects of somatostatin on the Kupffer cells in cirrhotic livers are not known. In the present study, Kupffer cells, obtained from male rats with carbon tetrachloride-induced cirrhotic livers, were treated in vitro with somatostatin or octreotide and their effects on the release of nitric oxide, tumor necrosis factor-alpha (TNF-alpha) and peroxide (H2O2) determined. At concentrations of 10(-13) or 10(-10) to 10(-6) M of somatostatin or 10(-12) to 10(-10) M, or 10(-6) M of octreotide, the amount of nitric oxide released by Kupffer cells was significantly suppressed relative to that of untreated cells. Kupffer cells treated with less than 10(-12) M or greater than 10(-12) M of somatostatin or octreotide released less TNF-alpha compared to the untreated controls. In addition, zymosan-induced H2O2 release by Kupffer cells treated with 10(-9) to 10(-7) M somatostatin or with 10(-15) to 10(-13) M and 10(-9) to 10(-7) M of octreotide was greater than that of the untreated controls. These findings demonstrate that somatostatin and octreotide modulate the release of nitric oxide, TNF-alpha and H2O2 by Kupffer cells in cirrhotic livers depending on the concentrations of hormones used.