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.
Turtinen
L W
LW
Department of Microbiology, Medical School, University of Minnesota, Minneapolis 55455.
Assimacopoulos
A
A
Haase
A T
AT
D001345:Autoradiography; D002470:Cell Survival; D003587:Cytomegalovirus / Q000254:growth & development / Q000276:immunology*; D006801:Humans; D007375:Interleukin-1 / Q000096:biosynthesis; D007700:Kinetics; D008070:Lipopolysaccharides / Q000378:metabolism / Q000494:pharmacology; D009000:Monocytes / Q000378:metabolism / Q000382:microbiology*; D015846:Monokines / Q000096:biosynthesis*; D009693:Nucleic Acid Hybridization; D012333:RNA, Messenger / Q000378:metabolism; D014407:Tumor Cells, Cultured; D014409:Tumor Necrosis Factor-alpha / Q000096:biosynthesis
D007375:Interleukin-1; D008070:Lipopolysaccharides; D015846:Monokines; D012333:RNA, Messenger; D014409:Tumor Necrosis Factor-alpha