SEPSIS AND ENDOTOXEMIA IN MICE STIMULATE THE EXPRESSION OF INTERLEUKIN-1 AND INTERLEUKIN-6 IN THE CENTRAL-NERVOUS-SYSTEM

1. In previous studies, experimental endotoxaemia was found to stimula te cytokine production in the central nervous system. The effect of se psis on brain cytokines is not fully known. We compared the effect of endotoxaemia and sepsis on brain interleukin-1 and interleukin-6 expre ssion. 2. Male A/J mice were injected subcutaneously with lipopolysacc haride (10 mg/kg) or an equal volume of saline as control. Sepsis was induced by caecal ligation and puncture (CLP); control mice underwent sham-operation. Brain tissue was assayed for interleukin-1 and interle ukin-6 by ELISA. Northern blotting or the polymerase chain reaction wa s used to determine cytokine mRNA levels. 3. Administration of endotox in induced a greater than fourfold increase in brain interleukin-1, a greater than threefold increase in interleukin 6 and an increase in mR NA for both cytokines. Caecal ligation and puncture resulted in increa sed brain interleukin-1 and interleukin-6 levels, but the changes were less pronounced and occurred later than after injection of endotoxin. There was no detectable difference in brain interleukin-1 mRNA betwee n septic and sham-operated mice, whereas interleukin-6 mRNA was increa sed in brains of septic animals. 4. Sepsis and endotoxaemia resulted i n similar, although not identical, changes in brain interleukin-1 and interleukin-6 concentrations and mRNA levels, suggesting that increase d cytokine production in the central nervous system is part of the sys temic response to sepsis and may be mediated by endotoxin.