Posttranscriptional Down‐Regulation of Tumor Necrosis Factor‐α and Interleukin‐1β 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.