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 behavior of hyperactivated monocytes following trauma is to fully understand the mechanistic basis of cellular dysfunction. It was the objective of this study to scrutinize the synthesis patterns and the level of regulation of the functionally related inflammatory cytokines interleukin (IL)-1 beta and IL-8 under stressful conditions. We compared the quantity of cytokine protein release in lipopolysaccharide-stimulated in vitro cultures of peripheral blood mononuclear leukocytes with the signal intensity of the corresponding detectable mRNAs. Fourteen patients with major burn or multiple trauma on consecutive days post-trauma and 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 thereafter. In contrast to IL-1 beta, a clear concurrence between mRNA signal intensity and the quantity of protein release was found in the majority 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 transcriptional level, whereas the downregulation of IL-1 beta occurs, most likely, on the post-transcriptional level.
Schinkel
C
C
Department of Surgery, Klinikum Grosshadern, Ludwig-Maximilians-University Munich, Germany.
Zimmer
S
S
Kremer
J P
JP
Walz
A
A
Rordorf-Adam
C
C
Henckel von Donnersmarck
G
G
Faist
E
E
D000293:Adolescent; D000328:Adult; D000368:Aged; D002056:Burns / Q000235:genetics / Q000503:physiopathology*; D005260:Female; D006801:Humans; D066298:In Vitro Techniques; D018836:Inflammation Mediators / Q000502:physiology; D007375:Interleukin-1 / Q000096:biosynthesis* / Q000235:genetics / Q000378:metabolism; D016209:Interleukin-8 / Q000096:biosynthesis* / Q000235:genetics / Q000378:metabolism; D008070:Lipopolysaccharides / Q000494:pharmacology; D008297:Male; D008875:Middle Aged; D009000:Monocytes / Q000187:drug effects / Q000502:physiology; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D013997:Time Factors; D014158:Transcription, Genetic; D014947:Wounds and Injuries / Q000235:genetics / Q000503:physiopathology*
D018836:Inflammation Mediators; D007375:Interleukin-1; D016209:Interleukin-8; D008070:Lipopolysaccharides; D012333:RNA, Messenger