PMID- 18046045
OWN - NLM
STAT- MEDLINE
DCOM- 20080303
LR  - 20211020
IS  - 1460-2377 (Electronic)
IS  - 0953-8178 (Print)
IS  - 0953-8178 (Linking)
VI  - 20
IP  - 1
DP  - 2008 Jan
TI  - Massive but selective cytokine dysregulation in the colon of IL-10-/- mice 
      revealed by multiplex analysis.
PG  - 141-54
AB  - IL-10-deficient mice develop enterocolitis due to a failure of cytokine 
      regulation; however, the full scope of that response remains poorly defined. 
      Using multiplex analysis to quantify the activity of 23 regulatory and effector 
      cytokines produced by colonic leukocytes, we demonstrate a vast dysregulation 
      process of 18 cytokines in IL-10-/- mice from 7 to 27 weeks of age. Of those, 
      IL-12p40, IL-6, granulocyte macrophage colony-stimulating factor, IFN-gamma, 
      IL-13 and monocyte chemoattractant protein-1 (MCP-1) had the highest single 
      correlations with pathology (r = 0.7766-0.7016). Importantly, there were strong 
      associations (r = 0.7071-0.9074) between those cytokines and as many as 10 
      additional cytokines, indicating a high degree of cytokine complexity as disease 
      progressed. IL-17 was notable in that it was produced at high levels by colonic 
      leukocytes from IL-10-/- mice with pathology ranging from mild to severe, though 
      it was not produced by healthy IL-10-/- mice lacking pathology. Tumor necrosis 
      factor alpha (TNFalpha) by itself displayed only a modest association with 
      pathology (r = 0.6340), ranking sixth lowest, though it cross-correlated strongly 
      with the synthesis of 12 other cytokines, implying that the destructive effects 
      associated with TNFalpha may be due to interactions of multiple cytokine 
      activities. IL-23 expression did not correlate with pathology, possibly 
      suggesting that IL-23 is involved in the initiation but not the perpetuation of 
      inflammation. Four cytokines (IL-2, IL-3, IL-4 and IL-5) remained negative in 
      IL-10-/- mice, demonstrating that cytokine dysregulation was not universal. These 
      findings emphasize the need to better understand cytokine networks in chronic 
      inflammation and they provide a rationale for combining immunotherapies in the 
      treatment of intestinal inflammation.
FAU - Montufar-Solis, Dina
AU  - Montufar-Solis D
AD  - Department of Diagnostic Sciences, Dental Branch, University of Texas Health 
      Science Center at Houston, 6516 MD Anderson Boulevard, Houston, TX, USA.
FAU - Schaefer, Jeremy
AU  - Schaefer J
FAU - Hicks, M John
AU  - Hicks MJ
FAU - Klein, John R
AU  - Klein JR
LA  - eng
GR  - R01 DK035566/DK/NIDDK NIH HHS/United States
GR  - R01 DK035566-22/DK/NIDDK NIH HHS/United States
GR  - DK035566/DK/NIDDK NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
DEP - 20071128
PL  - England
TA  - Int Immunol
JT  - International immunology
JID - 8916182
RN  - 0 (Cytokines)
RN  - 130068-27-8 (Interleukin-10)
SB  - IM
MH  - Animals
MH  - Colitis/*immunology/pathology/*physiopathology
MH  - Colon/cytology/immunology/*pathology
MH  - Cytokines/genetics/immunology/*metabolism
MH  - Epithelial Cells/cytology/immunology/*pathology
MH  - Female
MH  - Interleukin-10/*deficiency/genetics
MH  - Leukocytes/cytology/immunology/*pathology
MH  - Male
MH  - Mice
MH  - Mice, Inbred BALB C
PMC - PMC2756059
MID - NIHMS143711
EDAT- 2007/11/30 09:00
MHDA- 2008/03/04 09:00
PMCR- 2009/10/02
CRDT- 2007/11/30 09:00
PHST- 2007/11/30 09:00 [pubmed]
PHST- 2008/03/04 09:00 [medline]
PHST- 2007/11/30 09:00 [entrez]
PHST- 2009/10/02 00:00 [pmc-release]
AID - dxm126 [pii]
AID - 10.1093/intimm/dxm126 [doi]
PST - ppublish
SO  - Int Immunol. 2008 Jan;20(1):141-54. doi: 10.1093/intimm/dxm126. Epub 2007 Nov 28.