Increased monokines in cytomegalovirus infected myelomonocytic cell cultures

In an investigation of the role of monokines in CMV associated immunosuppression we document modulation of both TNF and IL-1 beta in CMV infected THP-1 cells. CMV infected cultures released almost two-fold more IL-1 beta protein and contained significantly higher IL-1 beta mRNA levels than uninfected cultures for 72-96 h after induction. In both CMV infected and uninfected cultures, significant amounts of IL-1 beta protein were not detected until 24 h post induction, while maximum amounts of TNF were detected in culture supernatants by 3 h post induction, suggesting that TNF may play a role in IL-1 beta induction. TNF levels subsequently declined but in infected cultures remained over 2.5-fold higher than controls through 96 h. The CMV alteration in the kinetics and extent of IL-1 beta release must be indirectly mediated by CMV since only 1% of THP-1 cells were infected. Most infected cells expressed CMV immediate early proteins but did not overexpress IL-1. We speculate that CMV infected cells release excess TNF or other stimulatory factors which increase IL-1 beta synthesis. Since IL-1 beta is increased, the decreased IL-1 'activity' described by others as an explanation in part for the immunosuppressive effects of infection may actually reflect alterations of IL-1 inhibitor levels during CMV infection.