Korean J Ophthalmol.  2011 Apr;25(2):73-76. 10.3341/kjo.2011.25.2.73.

Investigating the Relationship between Serum Interleukin-17 Levels and Systemic Immune-Mediated Disease in Patients with Dry Eye Syndrome

• Oh JY
• Kim MK
• Choi HJ
• Ko JH
• Kang EJ
• Lee HJ
• Wee WR
• Lee JH

• KMID: 1111866
• DOI: http://doi.org/10.3341/kjo.2011.25.2.73

Abstract

PURPOSE
To investigate the association between dry eye syndrome (DE) and serum levels of interleukin (IL)-17 in patients with systemic immune-mediated diseases.
METHODS
IL-17 and IL-23 levels were measured in the sera of patients whose tear production was <5 mm on the Schirmer test. Subjects included patients with chronic graft-versus-host disease (GVHD), rheumatoid arthritis (RA), Sjogren's syndrome (SS), systemic lupus erythematosus (SLE), and no systemic disease. Corneal/conjunctival fluorescein staining was scored and the correlation between the score and the IL-17 level was evaluated.
RESULTS
A strong correlation existed between IL-17 level and the type of systemic disease. IL-17 was significantly elevated in patients with chronic GVHD compared to those with RA and SS. IL-17 was not detectable in patients with SLE or in those without systemic disease. IL-23 was not detected in any of the subjects. IL-17 was significantly increased in patients with high fluorescein staining scores.
CONCLUSIONS
Our data suggest that IL-17 is involved in the pathogenesis of DE in patients with systemic immune-mediated diseases.

Keyword

Chronic graft-versus-host disease; Dry eye syndromes; Interleukin-17; Rheumatoid arthritis; Sjogren's syndrome

MeSH Terms

Adult
Biological Markers/blood
Conjunctiva/*pathology
Diagnosis, Differential
Dry Eye Syndromes/*blood/diagnosis/immunology
Enzyme-Linked Immunosorbent Assay
Female
Humans
*Immunity, Innate
Interleukin-17/*blood
Male
Middle Aged

Figure

• 

  Fig. 1 Levels of interleukin (IL)-17 in sera from dry eye patients with systemic diseases and dry eye subjects without systemic disease (control). GVHD = graft-versus-host disease; RA = rheumatoid arthritis; SLE = systemic lupus erythematosus.

Reference

1. Nguyen CQ, Hu MH, Li Y, et al. Salivary gland tissue expression of interleukin-23 and interleukin-17 in Sjogren's syndrome: findings in humans and mice. Arthritis Rheum. 2008. 58:734–743.

2. Sakai A, Sugawara Y, Kuroishi T, et al. Identification of IL-18 and Th17 cells in salivary glands of patients with Sjogren's syndrome, and amplification of IL-17-mediated secretion of inflammatory cytokines from salivary gland cells by IL-18. J Immunol. 2008. 181:2898–2906.

3. Garrett-Sinha LA, John S, Gaffen SL. IL-17 and the Th17 lineage in systemic lupus erythematosus. Curr Opin Rheumatol. 2008. 20:519–525.

4. Tesmer LA, Lundy SK, Sarkar S, Fox DA. Th17 cells in human disease. Immunol Rev. 2008. 223:87–113.

5. Chi W, Zhu X, Yang P, et al. Upregulated IL-23 and IL-17 in Behçet patients with active uveitis. Invest Ophthalmol Vis Sci. 2008. 49:3058–3064.

6. Amadi-Obi A, Yu CR, Liu X, et al. TH17 cells contribute to uveitis and scleritis and are expanded by IL-2 and inhibited by IL-27/STAT1. Nat Med. 2007. 13:711–718.

7. Abraham C, Cho J. Interleukin-23/Th17 pathways and inflammatory bowel disease. Inflamm Bowel Dis. 2009. 15:1090–1100.

8. Diveu C, McGeachy MJ, Cua DJ. Cytokines that regulate autoimmunity. Curr Opin Immunol. 2008. 20:663–668.

9. McGeachy MJ, Chen Y, Tato CM, et al. The interleukin 23 receptor is essential for the terminal differentiation of interleukin 17-producing effector T helper cells in vivo. Nat Immunol. 2009. 10:314–324.

10. Langrish CL, Chen Y, Blumenschein WM, et al. IL-23 drives a pathogenic T cell population that induces autoimmune inflammation. J Exp Med. 2005. 201:233–240.

11. Yen D, Cheung J, Scheerens H, et al. IL-23 is essential for T cell-mediated colitis and promotes inflammation via IL-17 and IL-6. J Clin Invest. 2006. 116:1310–1316.

12. Murphy CA, Langrish CL, Chen Y, et al. Divergent pro- and antiinflammatory roles for IL-23 and IL-12 in joint autoimmune inflammation. J Exp Med. 2003. 198:1951–1957.

13. Norn MS. Lissamine green. Vital staining of cornea and conjunctiva. Acta Ophthalmol (Copenh). 1973. 51:483–491.

14. Kappel LW, Goldberg GL, King CG, et al. IL-17 contributes to CD4-mediated graft-versus-host disease. Blood. 2009. 113:945–952.

15. De Paiva CS, Chotikavanich S, Pangelinan SB, et al. IL-17 disrupts corneal barrier following desiccating stress. Mucosal Immunol. 2009. 2:243–253.

16. Sutton CE, Lalor SJ, Sweeney CM, et al. Interleukin-1 and IL-23 induce innate IL-17 production from gammadelta T cells, amplifying Th17 responses and autoimmunity. Immunity. 2009. 31:331–341.

17. Mathers WD. Why the eye becomes dry: a cornea and lacrimal gland feedback model. CLAO J. 2000. 26:159–165.

18. Chauhan SK, El Annan J, Ecoiffier T, et al. Autoimmunity in dry eye is due to resistance of Th17 to Treg suppression. J Immunol. 2009. 182:1247–1252.