Cytokine mRNA Expression After Transient and Prolonged Hypotension

The role of cytokines in hemorrhagic shock remains controversial, with some studies showing an elevation of cytokines, whereas others do not. We thus analyzed the changes in tumor necrosis factor (TNF) activity and in mRNA of TNFα, interleukin-1β (IL-1β), and interleukin-6 (IL-6) after transient and prolonged hypotension. In the transient hypotension group (TH group), chronically cannulated rats were bled (20 ml/kg·3min) without fluid resuscitation. They showed transient hypotension, but their blood pressure (BP) quickly stabilized. In the prolonged hypotension group (PH group), the rats were bled and maintained at a mean BP of 40 mmHg for 60 min, and then were resuscitated with the shed, blood and an equal volume of saline over 60 min. The serum TNF activity was measured by cytotoxicity against the L929 tumorigenic murine fibroblast. Messenger RNA of TNFα, IL-1β, and IL-6 in liver was measured semi-quantitatively by high-performance liquid chromatography after reverse transcription and polymerase chain reaction. The increases in the TNF activity were not significant in either of the groups above the prehemorrhage levels, whereas mRNA of TNFα and IL-1β showed a transient elevation in the TH group and a persistent elevation in the TH group. IL-6 mRNA did not increase significantly in the TH group, but did increase in the PH group. These results show that a large hemorrhage induces cytokine mRNA in the liver and also show the differences in the changes of cytokine mRNA after transient and prolonged hypotension.