PMID- 14612201
OWN - NLM
STAT- MEDLINE
DCOM- 20040401
LR  - 20190718
IS  - 0021-9150 (Print)
IS  - 0021-9150 (Linking)
VI  - 170
IP  - 2
DP  - 2003 Oct
TI  - IL-6 is produced by splenocytes derived from CMV-infected mice in response to CMV 
      antigens, and induces MCP-1 production by endothelial cells: a new mechanistic 
      paradigm for infection-induced atherogenesis.
PG  - 223-8
AB  - Atherosclerosis is an inflammatory disease. One of the candidate inflammatory 
      triggers is infection. To further characterize the interaction between infection, 
      cytokine induction, and atherosclerosis, we tested the hypothesis that 
      cytomegalovirus (CMV) infection induces the pro-inflammatory cytokine 
      interleukin-6 (IL-6), which in turn induces "pro-atherosclerotic" changes in 
      vascular endothelial cells (ECs). ELISA was used to determine the levels of 
      monocyte chemoattractant protein-1 (MCP-1) in the supernatant of mouse and human 
      ECs incubated with IL-6, and IL-6 levels in supernatants of splenocytes, derived 
      from CMV-infected and uninfected mice, stimulated with mice CMV antigens. IL-6 
      induced, in a dose response fashion, MCP-1 expression in human ECs: 0, 2, 10, and 
      50 pg/ml IL-6 increased MCP-1 levels in EC conditioned medium from 1120+/-65 to 
      1148+/-105, 1395+/-40, and 2119+/-130 pg/ml, respectively (P<0.001). IL-6 also 
      induced MCP-1 expression in mouse ECs (P<0.002). Importantly, IL-6 concentration 
      in the supernatants of splenocytes stimulated with CMV antigens rose from 
      undetectable levels in uninfected mice to 14.9+/-5 pg/ml in the infected mice 
      (P<0.04). These results suggest a previously unrecognized, but potentially 
      important mechanism whereby CMV, and other pathogens, contribute to 
      atherogenesis: T lymphocytes, clonally expanded in response to antigens presented 
      by CMV infection, home to sites of vascular injury and locally release IL-6 when 
      presented with either pathogen antigens that may be present in the plaque, or 
      when they cross-react with host peptides homologous to the relevant pathogen 
      antigens; IL-6 then triggers ECs to release MCP-1, which recruits more monocytes 
      and T-cells into the vessel wall and thereby exacerbates local inflammation, and 
      thus atherogenesis.
FAU - Rott, David
AU  - Rott D
AD  - Cardiovascular Research Institute, Medstar Research Institute, Washington 
      Hospital Center, 108 Irving Street, NW, GHRB 217, 20010, Washington, DC, USA
FAU - Zhu, Jianhui
AU  - Zhu J
FAU - Zhou, Yi Fu
AU  - Zhou YF
FAU - Burnett, Mary Susan
AU  - Burnett MS
FAU - Zalles-Ganley, Alexandra
AU  - Zalles-Ganley A
FAU - Epstein, Stephen E
AU  - Epstein SE
LA  - eng
PT  - Journal Article
PL  - Ireland
TA  - Atherosclerosis
JT  - Atherosclerosis
JID - 0242543
RN  - 0 (Antibodies, Viral)
RN  - 0 (Antigens, Viral)
RN  - 0 (Chemokine CCL2)
RN  - 0 (Interleukin-6)
RN  - 82115-62-6 (Interferon-gamma)
SB  - IM
MH  - Animals
MH  - Antibodies, Viral/analysis
MH  - Antigens, Viral/*immunology
MH  - Arteriosclerosis/*virology
MH  - Cells, Cultured
MH  - Chemokine CCL2/*biosynthesis
MH  - Cytomegalovirus/immunology
MH  - Cytomegalovirus Infections/complications/immunology/*metabolism
MH  - Dose-Response Relationship, Drug
MH  - Endothelium, Vascular/*metabolism
MH  - Enzyme-Linked Immunosorbent Assay
MH  - Humans
MH  - Interferon-gamma/biosynthesis
MH  - Interleukin-6/*biosynthesis
MH  - Mice
MH  - Mice, Inbred C57BL
MH  - Mice, Knockout
MH  - Spleen/cytology/immunology/*metabolism
EDAT- 2003/11/13 05:00
MHDA- 2004/04/02 05:00
CRDT- 2003/11/13 05:00
PHST- 2003/11/13 05:00 [pubmed]
PHST- 2004/04/02 05:00 [medline]
PHST- 2003/11/13 05:00 [entrez]
AID - S0021-9150(03)00295-8 [pii]
AID - 10.1016/s0021-9150(03)00295-8 [doi]
PST - ppublish
SO  - Atherosclerosis. 2003 Oct;170(2):223-8. doi: 10.1016/s0021-9150(03)00295-8.