THE mRNA EXPRESSION AND IN VITRO PRODUCTION OF CYTOKINES AND OTHER PROTEINS BY HEPATOCYTES AND KUPFFER CELLS FOLLOWING THERMAL INJURY

Abstract

Inflammatory cytokines and acute-phase proteins are closely interrelated, and their levels of production by various cells are increased by thermal injury. It was hypothesized that burn-mediated increases in the production of TNF and IL-6 by Kupffer cells and the production of acute phase proteins by hepatocytes are paralleled by increases in the corresponding message RNA levels in these cells. The mRNA expression of the cytokines, IL-6 and TNF alpha, and acute phase proteins, alpha-1 acid glycoprotein (alpha-1 AGP), and albumin in liver tissue were determined in rats 24 h after thermal injury. Also IL-6 and TNF alpha from in vitro cultured Kupffer cells, and alpha-1 AGP and albumin from in vitro 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 released from cultured Kupffer cells and by increased serum levels of this cytokine. Thermal injury caused a decrease in TNF mRNA but no change 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 expression following thermal injury was consistent with the increase of alpha-1 AGP production by hepatocytes and with the elevated serum level of 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 results suggest that thermal injury may cause alterations in the cytokine and acute phase protein mRNA levels in liver, which may cause alterations in the cellular production and serum levels of the corresponding proteins.(ABSTRACT TRUNCATED AT 250 WORDS)