The influence of major trauma on the regulatory levels of interleukin-1 (IL-1) and IL-2 in human mononuclear leukocytes.
The monokine Interleukin-1 (IL-1) and the lymphokine IL-2 are playing a crucial role within the course of an intact cell mediated immune response (CMI). It was the objective of this study to further elucidate the cytokine associate mechanisms of dysfunctional T-cell activation following major burn and mechanical trauma. Via comparative analysis of mRNA expression and protein release the major regulatory levels of IL-1 and IL-2 release under stressful conditions were to be determined in mitogen respectively LPS stimulated PBMC (peripheral blood mononuclear cells) cultures on consecutive days (D) 1, 3, 5, 7 and 10 post injury. Further, we wanted to scrutinize if inadequate IL-2 production post-trauma is possible due to a defective transduction of extracellular signals to the T-cell nucleus. In order to answer this question IL-2 mRNA expression and IL-2 protein releases were determined in PBMC cultures using the phosphokinase C (PKC) activator phorbol ester (PMA) as a costimulus together with PHA. When analyzing the cumulative data for IL-1 beta we saw until D 5 post-trauma a considerable impairment of the protein release in LPS stimulated PBMC cultures and recovery thereafter. In only a few individual PBMC cultures we saw a concurrence between the IL-1 beta mRNA signal intensity and the protein production. In the majority of the autoradiographies analyzed, the mRNA expression for IL-1 beta was considerably more distinct compared to controls while the corresponding protein release values were on control level or below. These results implicate that the suppression of IL-1 beta post-trauma is regulated mainly on a posttranscriptional level. Since Prostaglandin E2 (PGE2) has been found to have a vigorous impact on the IL-1 beta synthesis on the translational level, we assume that the high PGE2 levels post-trauma inhibit--via cAMP--sufficient IL-1 beta synthesis on the posttranscriptional level. IL-2 protein synthesis as well as mRNA expression in mitogen (PHA) stimulated PBMC cultures following trauma, was persistently and significantly depressed compared to controls during the time of observation. The addition of PMA as a costimulus to PHA, could induce very distinct mRNA signals for IL-2 with a signal intensity which was comparable to that found in the cells of healthy controls. Also the quantity of IL-2 protein release in the vast majority of all patients PBMC cultures following PHA/PMA induction was within the control range.(ABSTRACT TRUNCATED AT 400 WORDS)
Department of Surgery, University of Munich.
E
E
Faist
C
C
Schinkel
S
S
Zimmer
J P
JP
Kremer
S
S
Alkan
C
C
Rordorf
H
H
von Donnersmarck
F W
FW
Schildberg
D000293:Adolescent; D000328:Adult; D000368:Aged; D002056:Burns / Q000276:immunology*; D005260:Female; D006801:Humans; D007108:Immune Tolerance / Q000276:immunology; D016130:Immunophenotyping; D007362:Intensive Care Units; D007375:Interleukin-1 / Q000097:blood*; D007376:Interleukin-2 / Q000097:blood*; D008213:Lymphocyte Activation / Q000276:immunology*; D008297:Male; D008875:Middle Aged; D009000:Monocytes / Q000276:immunology*; D009104:Multiple Trauma / Q000276:immunology*; D009894:Opportunistic Infections / Q000276:immunology; D012307:Risk Factors; D015398:Signal Transduction / Q000502:physiology; D013601:T-Lymphocytes / Q000276:immunology*
D007375:Interleukin-1; D007376:Interleukin-2