THE MESSENGER-RNA EXPRESSION AND IN-VITRO PRODUCTION OF CYTOKINES ANDOTHER PROTEINS BY HEPATOCYTES AND KUPFFER CELLS FOLLOWING THERMAL-INJURY

Inflammatory cytokines and acute-phase proteins are closely interrelat ed, and their levels of production by various cells are increased by t hermal injury. It was hypothesized that burn-mediated increases in the production of TNF and IL-6 by Kupffer cells and the production of acu te phase proteins by hepatocytes are paralleled by increases in the co rresponding message RNA levels in these cells. The mRNA expression of the cytokines, IL-6 and TNF alpha, and acute phase proteins, alpha-1 a cid glycoprotein alpha-1 AGP), and albumin in liver tissue were determ ined in rats 24 h after thermal injury. Also IL-6 and TNF(alpha from i n vitro cultured Kupffer cells, and alpha-1 AGP and albumin from in vi tro cultured hepatocytes, and the serum levels of these proteins, were determined. An increased expression of IL-6 mRNA in liver tissue from animals of the burned group was accompanied by an elevation of IL-6 r eleased from cultured Kupffer cells and by increased serum levels of t his cytokine. Thermal injury caused a decrease in TNF mRNA but no chan ge in the production of this cytokine by Kupffer cells, and TNF could not be found in the serum. Also, an increase in alpha-1 AGP mRNA expre ssion following thermal injury was consistent with the increase of alp ha-1 AGP production by hepatocytes and with the elevated serum level o f this acute phase protein. Thermal injury caused no change in albumin mRNA expression or in the in vitro production of this negative acute phase protein, however, the serum level of albumin increased. The resu lts suggest that thermal injury may cause alterations in the cytokine and acute phase protein mRNA levels in liver, which may cause alterati ons in the cellular production and serum levels of the corresponding p roteins. An increase in IL-6 production, mediated by thermal injury, m ay be beneficial to the immune response but may lead to an overwhelmin g inflammatory response.