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IL6 - Interleukin 6

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About Interleukin 6 (IL6)

Interleukin 6, IL6, a signaling molecule of the Immune System. Specifically, IL6 is a Cytokine expressed following NOD2 activation at higher levels in cells with ATG16L1 - Autophagy Related 16 Like 1 mutation (*300A) than cells with non-mutated ATG16L1.

- Increased levels of IL6 is associated with:
---- Aluminum Exposure
---- Anemia / Anaemia
---- Bone Absorption / Blockage of New Bone Formation / Osteoperosis
---- Claudin-2 Expression (Increased)
---- Colitis
---- Depression
---- Fatigue
---- Infection
---- Inflammation
---- Permeability (Leakiness) of Tight Junctions to Cations (sp. Sodium Ions)
---- Sleep
---- Weight Loss
---- Wound Repair [3]

- High levels of IL6 increase the risk of Cardiovascular Disease

- High levels of IL6 in the eye are associated with diabetes-related eye disease (macular edema).

- IL6 levels are increased during periods of chronic stress

- IL6 levels increase in Serum during certain stages of Sleep (Stages 1,2 and REM).[4]

Interleukin 6 and Inflammatory Bowel Disease

The Inflammatory Bowel Diseases (IBD), Crohn's Disease (CD) and Ulcerative Colitis (UC), have differing involvement of IL6.

- IL-6 is Increased in Patients with Active Crohn's Disease [2]

- IL-6 is Not Increased in Ulcerative Colitis [2]

IL6 and Crohn's Disease

Interleukin 6 (IL6) is located on Chromosome 7p15.3
Childhood (pediatric) - onset Crohn's Disease occurs more often in males than females. Adult onset Crohn's Disease occurs more often in females. It is suggested there may be a hormone based link (estrogen and estrogen receptor) to this sex difference.
- In male children the IL6 promotor region sequence (IL6 -174) affects age of onset of Crohn's Disease.[6]

- Estrogen and Estrogen Receptors reduce IL6 expression through the Promotor region.

Treatments Involving Interleukin 6

- TNF increases IL6 levels. This induction can be reduced, with subsequent reduction in IL6 levels, by Anti - TNF treatments such as Remicade / Infliximab, Humira / Adalimumab, Cimzia, etc.

- Lutein administration has an anti-inflammatory effect on experimentally-produced Uveitis in rodents.[5]
Uveitis was induced by the bacterial cell wall component, Lipopolysaccharide (LPS). Following LPS administration multiple pro-inflammatory factors increased, including IL6. Animals given Lutein had reduced levels of inflammatory factors including: IL6, MCP-1, MCP-2, PGE2, TNF - Alpha. Lutein (100 mg/kg) treatment produced a similar anti-inflammatory effect to Dexamethasone.[5]

Other Cytokines in IBD

Check out the Wiki page listing other Cytokines involved in IBD HERE.

For More Genes Implicated in IBD

For More Genes Implicated in Inflammatory Bowel Diseases please see our Wiki Entry Genes and IBD

References

1. http://www.google.com/url?sa=t&rct=j...IS7M0xsTloEMCQ

2. Mahida YR, Kurlac L, Gallagher A, and Hawkey CJ. High circulating concentrations of interleukin-6 in active Crohn's disease but not ulcerative colitis. Gut 1991; 32(12): 1531-1534 doi:10.1136/gut.32.12.1531 http://gut.bmj.com/content/32/12/1531.full.pdf+html

3. Lin Z-Q, Kondo T, Ishida Y, Takayasu T, and Mukaida N. Essential involvement of IL-6 in the skin wound-healing process as evidenced by delayed wound healing in IL-6-deficient mice. J Leukoc Biol. 2003; 73 (6):713-721. http://www.jleukbio.org/content/73/6/713.full.pdf+html

4. Redwine, L., Hauger, R. L., Gillin, J. C., Irwin, M. Effects of sleep and sleep deprivation on interleukin-6, growth hormone, cortisol, and melatonin levels in humans. J. Clin. Endocr. Metab. 2000; 85: 3597-3603. http://jcem.endojournals.org/content....full.pdf+html

5. Jin XH, Ohgami K, Shiratori K, Suzuki Y, Hirano T, Koyama Y, Yoshida K, Ilieva I, Iseki K, and Ohno S. Inhibitory effects of lutein on endotoxin-induced uveitis in Lewis rats. Invest Ophthalmol Vis Sci. 2006; 47(6): 2562-2568. http://www.iovs.org/content/47/6/2562.full.pdf+html

6. Sagiv-Friedgut K, Karban A, Weiss B, et al. Early-onset Crohn disease is associated with male sex and a polymorphism in the IL-6 promoter. J Pediatric Gastroenterol Nutr. 2010; 50(1): 22-26. http://journals.lww.com/jpgn/Fulltex...h_Male.10.aspx

7. Suzuki T, Yoshinaga N, Tanabe S. Interleukin-6 (IL-6) Regulates Claudin-2 Expression and Tight Junction Permeability in Intestinal Epithelium. J Biol Chem. 2011; 286(36): 3126331271. http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3173073

8. Carey R, Jurickova I, Ballard E, Bonkowski E, Han X, Xu H, Denson. Activation of an IL-6:STAT3-dependent Transcriptome in Pediatric-onset Inflammatory Bowel Disease. Inflamm Bowel Dis. 2008; 14(4): 446-457. http://www.ncbi.nlm.nih.gov/pmc/arti...ihms-76393.pdf

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