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 admi nistration of chlortetracycline (CTC) on ex vivo perfused pig livers. The r etention and clearance of Salmonella choleraesuis, production of acute phas e 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 Sal monella LPS 24 h before removal of the liver. Salmonella retention and clea rance by livers of pigs given CTC was lower than by control livers (p < 0.0 1 and p < 0.05, respectively). We demonstrated an increase of CRP and HPG b y livers from control pigs after a three-hour perfusion while pigs from CTC pretreated pigs varied in this response. Further, CTC decreased the secret ion of TNF-alpha by cultured KC incubated in vitro with LPS. Modulation of TNF-alpha production by CTC suggests a potential for attenuating the inflam matory response. However, this possible beneficial action of CTC was accomp anied by a significant decline in the antimicrobial effect of the liver. (C ) 2001 Elsevier Science Ltd. All rights reserved.