CYTOKINE RELEASE BY PORCINE LIVERS PERFUSED WITH LIPOPOLYSACCHARIDE OR LIVE SALMONELLA-CHOLERAESUIS

Objective-To develop a model to study the kinetics and relative amount s of cytokines produced by liver cells during enteric infection. Desig n-Salmonella enteriditis lipopolysaccharide (LPS)-or live S choleraesu is-stimulated isolated livers from clinically normal pigs and pigs wit h active acute phase response. Animals-7- to 14-day-old salmonellosis- free pigs, 4 to 12/group. Procedure-Livers were removed and perfused w ith oxygenated Krebs-Henseleit solution for 30 minutes and with S chol eraesuis or LPS added for 7 minutes. Livers were then perfused with 50 0 ml of fresh solution in a closed loop procedure for 180 minutes. Per fusate samples were collected for tumor necrosis factor-alpha (TNF alp ha) and interleukin 6 (IL-6) bioassays. Results-Tumor necrosis factor- alpha values remained constant during perfusion of normal livers and i ncreased in those exposed to LPS. Interleukin 6 values increased in pe rfusate from normal livers from 30 to 150 minutes, then decreased. In livers from pigs with an active acute phase response, TNF alpha values were reduced; IL-6 appeared by 2 minutes and decreased after 25 minut es. Conclusions-Isolated livers could be kept viable for 3 hours, and IL-6 and TNF alpha could be measured by the bioassays used. Clinical R elevance-Model can be used for studying and modifying the response of liver cells to infective agents.