TNF GENE-EXPRESSION IN MONOCYTES OF LOW AND HIGH RESPONDER INDIVIDUALS

Individuals with a consistently loner immune response may be more susc eptible to infection but less prone to autoimmune disease or severe se psis, The molecular mechanisms determining the low responder status ar e, however, unclear. We have screened 60 male donors for tumour necros is factor (TNF) protein levels after stimulation of monocytes with lip opolysaccharide (LPS). Among these we identified three donors each tha t consistently had a level of less than 20% (low responders; LR) or of more than 80% (high responders; HR) of the maximum response seen in t his population, Northern blot analysis of TNF mRNA after LPS stimulati on revealed lower transcript levels in LR. Half life determination aft er actinomycin D blockade showed a similar decay rate for LR and MR an d after blockade of degradation by cycloheximide treatment mRNA levels increased hut LR remained lower compared to HR. These data indicate t hat the lower TNF mRNA levels in Lit are not due to a more rapid mRNA degradation but rather a result of lower transcription, Transcripts fo r interleukin 6 (IL-6) were also low in LPS-stimulated monocytes of LR . Because expression of the LPS receptor CD14 was similar in LR and HR monocytes, our data suggest that differences in signal transduction a ccount for the LR and HR phenotype. (C) 1997 Academic Press Limited.