April 2009
Volume 50, Issue 13
Free
ARVO Annual Meeting Abstract  |   April 2009
IL-17 Neutralization Mutes Inflammation in a Mouse Model of Experimental Autoimmune Lacrimal Keratoconjunctivitis
Author Affiliations & Notes
  • M. E. Stern
    Biological Sciences, Allergan, Inc, Irvine, California
  • K. F. Siemasko
    Biological Sciences, Allergan, Inc, Irvine, California
  • C. S. Schaumburg
    Biological Sciences, Allergan, Inc, Irvine, California
  • J. Gao
    Biological Sciences, Allergan, Inc, Irvine, California
  • C. S. De Paiva
    Cullen Eye Institute, Baylor College of Medicine, Houston, Texas
  • M. Calonge
    IOBA, University of Valladolid, Valladolid, Spain
  • V. L. Calder
    Ophthalmology, University College London, Irvine, United Kingdom
  • L. A. Wheeler
    Biological Sciences, Allergan, Inc, Irvine, California
  • J. Y. Niederkorn
    Ophthalmology, University of Texas Southwestern Medical Center, Dallas, Texas
  • S. C. Pflugfelder
    Cullen Eye Institute, Baylor College of Medicine, Houston, Texas
  • Footnotes
    Commercial Relationships  M.E. Stern, Allergan, Inc., E; K.F. Siemasko, Allergan, Inc., E; C.S. Schaumburg, Allergan, Inc., E; J. Gao, Allergan, Inc., E; C.S. De Paiva, None; M. Calonge, Allergan, Inc., C; V.L. Calder, Allergan, Inc., C; L.A. Wheeler, Allergan, Inc., E; J.Y. Niederkorn, Allergan, Inc., C; S.C. Pflugfelder, Allergan, Inc., C.
  • Footnotes
    Support  None.
Investigative Ophthalmology & Visual Science April 2009, Vol.50, 3653. doi:
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      M. E. Stern, K. F. Siemasko, C. S. Schaumburg, J. Gao, C. S. De Paiva, M. Calonge, V. L. Calder, L. A. Wheeler, J. Y. Niederkorn, S. C. Pflugfelder; IL-17 Neutralization Mutes Inflammation in a Mouse Model of Experimental Autoimmune Lacrimal Keratoconjunctivitis. Invest. Ophthalmol. Vis. Sci. 2009;50(13):3653.

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      © ARVO (1962-2015); The Authors (2016-present)

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Abstract

Purpose: : To evaluate the effect of IL-17 neutralization on the immunopathogenesis of experimental autoimmune lacrimal keratoconjunctivitis (ALKC).

Methods: : Experimental ALKC was induced in female C57BL/6 wild-type (WT) mice exposed to desiccating stress (DS: subcutaneous scopolamine (0.5 mg/0.2ml) TID, humidity <40%, and sustained airflow from fans positioned on both sides of cages screened with wire mesh) for 10 days. Mice were also injected intraperitoneally with 500 µg of anti-IL-17 antibody or rat isotype control starting 3 days before exposure to DS and on days 1, 3 and 7 post-DS. On day 10, mice were sacrificed and tears were collected for cytokine analysis. CD4+ T cells were also isolated from the spleen and superficial cervical lymph nodes of mice exposed to 10 days of DS in the presence and absence of anti-IL-17 antibody or rat isotype control and adoptively transferred to syngeneic T cell-deficient nude recipient mice that were not administered anti-IL-17 antibody. On day 3 post-adoptive transfer, tears and ocular surface tissues were collected from nude recipient mice for analysis of cytokine levels and histopathology.

Results: : WT C57BL/6 mice exposed to DS for 10 days displayed significantly elevated tear (p=0.042) and serum (p=0.0001) levels of IL-17 compared to control mice. In contrast, mice treated with anti-IL-17 (days -3, 1, 3, and 7) showed muted tear cytokine levels of IL-17 (p=0.03) and TNF- (p=0.03) relative to mice that received isotype control antibody. Adoptive transfer of CD4+ T cells from DS mice also yielded enhanced levels of IL-17 in tears (p=0.021); however, nude recipient’s of CD4+ T cells from anti-IL-17-treated donor mice showed low levels of IL-17 (p=0.048) and TNF- (p=0.023) in tears at 3-days post-transfer that were similar to baseline levels observed in nude control mice.

Conclusions: : These results indicate that IL-17 production is increased in mice with ALKC and can be perpetuated in nude recipient mice following adoptive transfer of DS-specific CD4+ T cells. Neutralizing IL-17 antibody decreased inflammation in mice exposed to desiccating stress suggesting that IL-17 is an important player in the immunopathogenesis of ALKC.

Keywords: cornea: tears/tear film/dry eye • cytokines/chemokines • conjunctiva 
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