Chlortetracycline modulates acute phase response of ex vivo perfused pig livers, and inhibits TNF-alpha secretion by isolated Kupffer cells.

Tetracyclines have been shown to have anti-inflammatory effects in addition to their antimicrobial action. We investigated the effects of in vivo administration of chlortetracycline (CTC) on ex vivo perfused pig livers. The retention and clearance of Salmonella choleraesuis, production of acute phase proteins C-reactive protein (CRP), and haptoglobin (HPG) by whole livers were studied. The in vitro modulation by CTC of TNF-alpha secretion by pig Kupffer cells (KC) was also studied. Pigs were dosed orally with CTC for three days, and given injections of Salmonella LPS 24 h before removal of the liver. Salmonella retention and clearance by livers of pigs given CTC was lower than by control livers (p < 0.01 and p < 0.05, respectively). We demonstrated an increase of CRP and HPG by livers from control pigs after a three-hour perfusion while pigs from CTC pretreated pigs varied in this response. Further, CTC decreased the secretion of TNF-alpha by cultured KC incubated in vitro with LPS. Modulation of TNF-alpha production by CTC suggests a potential for attenuating the inflammatory response. However, this possible beneficial action of CTC was accompanied by a significant decline in the antimicrobial effect of the liver.