Posttranscriptional down-regulation of tumor necrosis factor-alpha and interleukin-1beta production in acute meningococcal infections.
The regulation of tumor necrosis factor-alpha (TNF) and interleukin-1beta (IL-1beta) production was studied in patients with meningococcal disease. Circulating TNF and IL-1beta normalized within 1 day. TNF mRNA and IL-1beta mRNA in white blood cells decreased over 3-4 days. During the acute stage, TNF and IL-1beta production in stimulated whole blood cultures was down-regulated. After 4-5 days, this production was restored. The down-regulation was unlikely to be caused by circulating IL-6 and IL-10, as these cytokines normalized within 2-3 days. TNF mRNA in stimulated cultures during the acute stage, with down-regulated production, did not differ from that at recovery, with restored production. In contrast, the down-regulated production of IL-1beta was associated with significantly lower IL-1beta mRNA levels. Thus, TNF and IL-1beta production are differentially regulated. Whereas TNF production is regulated posttranscriptionally, IL-1beta production is also regulated at the mRNA level.
van Deuren
M
M
Department of Internal Medicine, University Hospital Nijmegen, The Netherlands.
Netea
M G
MG
Hijmans
A
A
Demacker
P N
PN
Neeleman
C
C
Sauerwein
R W
RW
Bartelink
A K
AK
van der Meer
J W
JW
D000900:Anti-Bacterial Agents / Q000627:therapeutic use; D002478:Cells, Cultured; D003907:Dexamethasone / Q000627:therapeutic use; D005786:Gene Expression Regulation; D006801:Humans; D007375:Interleukin-1 / Q000096:biosynthesis* / Q000097:blood; D007962:Leukocytes / Q000276:immunology*; D008589:Meningococcal Infections / Q000097:blood / Q000188:drug therapy / Q000276:immunology*; D014176:Protein Biosynthesis; D012333:RNA, Messenger / Q000097:blood; D012016:Reference Values; D013997:Time Factors; D014158:Transcription, Genetic; D014409:Tumor Necrosis Factor-alpha / Q000096:biosynthesis* / Q000378:metabolism; D001613:beta 2-Microglobulin / Q000096:biosynthesis
D000900:Anti-Bacterial Agents; D007375:Interleukin-1; D012333:RNA, Messenger; D014409:Tumor Necrosis Factor-alpha; D001613:beta 2-Microglobulin; D003907:Dexamethasone