POSTTRANSCRIPTIONAL DOWN-REGULATION OF TUMOR-NECROSIS-FACTOR-ALPHA AND INTERLEUKIN-1-BETA PRODUCTION IN ACUTE MENINGOCOCCAL INFECTIONS

The regulation of tumor necrosis factor-alpha (TNF) and interleukin-1 beta (IL-1 beta) production was studied in patients with meningococcal disease. Circulating TNF and IL-1 beta normalized within 1 day, TNF m RNA and IL-1 beta mRNA in white blood cells decreased over 3-4 days. D uring the acute stage, TNF and IL-1 beta production in stimulated whol e blood cultures was down-regulated. After 4-5 days, this production w as restored, The down-regulation was unlikely to be caused by circulat ing IL-6 and IL-10, as these cytokines normalized within 2-3 days. TNF mRNA in stimulated cultures during the acute stage, with down-regulat ed production, did not differ from that at recovery, with restored pro duction, In contrast, the down-regulated production of IL-1 beta was a ssociated with significantly lower IL-1 beta mRNA levels. Thus, TNF an d IL-1 beta production are differentially regulated. Whereas TNF produ ction is regulated posttranscriptionally, IL-1 beta production is also regulated at the mRNA level.