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The immunomodulatory effect of topical cyclosporin A in atopic keratoconjunctivitis
M Hingorani1, V L Calder, R J Buckley
1Moorfields Eye Hospital and the Department of Clinical Ophthalmology, Institute of Ophthalmology, London, United Kingdom.
Purpose:
To perform a detailed examination of the immunomodulatory effects of topical cyclosporin A (CsA) in conjunctival tissue from patients with atopic keratoconjunctivitis (AKC).
Methods:
Patients with active AKC were randomly allocated into two groups of four patients. For 3 months one group received 2% CsA drops, and the other group received placebo drops. Superior tarsal conjunctival biopsy specimens were harvested before and after treatment and examined by one- and two-color immunohistochemistry to compare leukocyte counts, HLA-DR+ and IL-2R+ cell counts, HLA-DR positivity of conjunctival epithelial cells, and counts of T cells expressing the cytokines interleukin (IL)-2, IL-3, IL-4, IL-5, and interferon (IFN)-gamma.
Results:
Posttreatment values were significantly less than pretreatment values for the total number of leukocytes and in the numbers of CD3+ T cells, CD4+ cells, CD8+ cells, CD20+ B cells, neutrophils, and macrophages, and there was a decrease in the CD4-CD8 ratio (P = 0.03) in the CsA group. There was a reduction from before CsA treatment to after CsA-treatment in the numbers of HLA-DR+ and IL-2R+ cells (P = 0.03), but the reduction in the epithelial cell HLA-DR expression did not reach significance. The number of T cells staining for IL-3 and IL-5 was reduced, although not to statistical significance, but there was a significant reduction in the number of T cells expressing IL-2 and IFN-gamma (P = 0.03) after CsA treatment compared with initial values. There were no statistically significant differences between pretreatment and posttreatment values in the placebo group. There was a clinical improvement in the CsA group and a clinical worsening in the placebo group.
Conclusions:
The in vitro effects of CsA translate into a reduction in T cells, a normalization of the CD4-CD8 ratio, a decrease in T-cell activation, and a reduction in T-cell cytokine expression, especially IL-2 and IFN-gamma. The decrease in HLA-DR expression may be mediated by the change in IFN-gamma. There were fewer B cells but not fewer plasma cells after CsA and no change in IL-4 expression, suggesting minimal effects on type I hypersensitivity responses. There was no significant reduction in mast cell or eosinophil numbers, but direct effects of topical CsA on their function may play a role in the therapy of ocular allergic disease. These results show that the beneficial effects of topical CsA in AKC are accompanied by important changes in conjunctival immune cell profiles.
Insights
Topical cyclosporin A (CsA) significantly reduced T cells, normalized the CD4-CD8 ratio, and decreased T-cell activation and cytokine expression in patients with atopic keratoconjunctivitis (AKC). These changes correlate with clinical improvement, demonstrating CsA
Area of Science:
- Immunology
- Ophthalmology
- Pharmacology
Background:
- Atopic keratoconjunctivitis (AKC) is a chronic allergic eye disease characterized by significant ocular inflammation.
- Topical immunomodulators are explored for managing AKC, but their precise effects on conjunctival immune cells require detailed investigation.
Purpose of the Study:
- To elucidate the immunomodulatory effects of topical cyclosporin A (CsA) on conjunctival immune cells in patients with active atopic keratoconjunctivitis (AKC).
Main Methods:
- A randomized controlled trial involving 8 AKC patients treated with 2% CsA drops or placebo for 3 months.
- Conjunctival biopsy specimens were analyzed pre- and post-treatment using immunohistochemistry to quantify various immune cell populations and cytokine expression (IL-2, IL-3, IL-4, IL-5, IFN-gamma).
Main Results:
- Topical CsA significantly reduced total leukocytes, T cells (CD3+, CD4+, CD8+), B cells (CD20+), neutrophils, and macrophages.
- CsA treatment led to a significant decrease in T-cell activation markers (HLA-DR+, IL-2R+) and expression of IL-2 and IFN-gamma.
- The CD4-CD8 ratio was normalized, and clinical improvement was observed in the CsA group, unlike the placebo group.
Conclusions:
- Topical CsA effectively modulates conjunctival immunity in AKC by reducing T-cell infiltration, activation, and pro-inflammatory cytokine production (IL-2, IFN-gamma).
- The observed immunomodulatory effects of CsA correlate with clinical benefits in AKC, suggesting its therapeutic potential.
- While CsA impacts T-cell responses, its effects on B cells and type I hypersensitivity mediators appear minimal, warranting further investigation into its role in mast cell and eosinophil function.