COMPARATIVE-ANALYSIS OF TRANSCRIPTION AND PROTEIN RELEASE OF THE INFLAMMATORY CYTOKINES INTERLEUKIN-1-BETA (IL-1-BETA) AND INTERLEUKIN-8 (IL-8) FOLLOWING MAJOR BURN AND MECHANICAL TRAUMA

The precondition for the systematic modulation of host impairing behav ior of hyperactivated monocytes following trauma is to fully understan d the mechanistic basis of cellular dysfunction. It was the objective of this study to scrutinize the synthesis patterns and the level of re gulation of the functionally related inflammatory cytokines interleuki n (IL)-1 beta and IL-8 under stressful conditions. We compared the qua ntity of cytokine protein release in lipopolysaccharide-stimulated in vitro cultures of peripheral blood mononuclear leukocytes with the sig nal intensify of the corresponding detectable mRNAs. Fourteen patients with major burn or multiple trauma on consecutive days post-trauma an d healthy volunteers were studied. We saw an almost identical pattern of synthesis for both monokines during the time of observation, with a considerable impairment until day 5 post-trauma and recovery thereaft er. In contrast to IL-1 beta, a clear concurrence between mRNA signal intensity and the quantity of protein release was found in the majorit y of patients for IL-8. From these data we conclude that the launching mechanisms for the de novo synthesis for both monokines under stress differ greatly, with IL-8 being clearly regulated on the transcription al level, whereas the downregulation of IL-1 beta occurs, most likely, on the post-transcriptional level.