High-throughput mRNA profiling characterizes the expression of inflammatory molecules in sepsis caused by Burkholderia pseudomallei.
Sepsis is characterized by an uncontrolled inflammatory response to invading microorganisms. We describe the inflammatory mRNA profiles in whole-blood leukocytes, monocytes, and granulocytes using a multigene system for 35 inflammatory markers that included pro- and anti-inflammatory cytokines, chemokines, and signal transduction molecules in a case-control study with 34 patients with sepsis caused by the gram-negative bacterium Burkholderia pseudomallei (the pathogen causing melioidosis) and 32 healthy volunteers. Relative to healthy controls, patients with sepsis showed increased transcription of a whole array of inflammatory genes in peripheral blood leukocytes, granulocytes, and monocytes. Specific monocyte and granulocyte mRNA profiles were identified. Strong correlations were found between inflammatory mRNA expression levels in monocytes and clinical outcome. These data underline the notion that circulating leukocytes are an important source for inflammatory mediators in patients with gram-negative sepsis. Gene profiling such as was done here provides an excellent tool to obtain insight into the extent of inflammation activation in patients with severe infection.
Wiersinga
W Joost
WJ
Academic Medical Center, Meibergdreef 9, Room G2-132, 1105 AZ Amsterdam, The Netherlands. w.j.wiersinga@amc.uva.nl
Dessing
Mark C
MC
Kager
Piet A
PA
Cheng
Allen C
AC
Limmathurotsakul
Direk
D
Day
Nicholas P
NP
Dondorp
Arjen M
AM
van der Poll
Tom
T
Peacock
Sharon J
SJ
D000328:Adult; D016957:Burkholderia pseudomallei / Q000502:physiology*; D005260:Female; D020869:Gene Expression Profiling; D006801:Humans; D018836:Inflammation Mediators / Q000378:metabolism*; D008297:Male; D008554:Melioidosis / Q000235:genetics / Q000276:immunology / Q000378:metabolism / Q000382:microbiology; D008875:Middle Aged; D012333:RNA, Messenger / Q000378:metabolism; D018805:Sepsis / Q000097:blood / Q000378:metabolism* / Q000382:microbiology
D018836:Inflammation Mediators; D012333:RNA, Messenger