The immunomodulatory effect of topical cyclosporin A in atopic keratoconjunctivitis

PURPOSE TO perform a detailed examination of the immunomodulatory effects o f topical cyclosporin A (CsA) in conjunctival tissue from patients with ato pic keratoconjunctivitis (AKC). METHODS. Patients with active AKC were randomly allocated into two groups o f four patients. For 3 months one group received 2% CsA drops, and the othe r group received placebo drops. Superior tarsal conjunctival biopsy specime ns were harvested before and after treatment and examined by one- and two-c olor immunohistochemistry to compare leukocyte counts, HLA-DR+ and IL-2R(+) cell counts, HLA-DR positivity of conjunctival epithelial cells, and count s of T cells expressing the cytokines interleulkin (IL)-2, IL-3, IL-4, IL-5 , and interferon (IFN)-gamma. RESULTS. Posttreatment values were significantly less than pretreatment val ues 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 numb er of T cells staining for IL-3 and IL-5 was reduced, although not to stati stical 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 compa red with initial values. There were no statistically significant difference s between pretreatment and posttreatment values in the placebo group. There was a clinical improvement in the CsA group and a clinical worsening in th e placebo group. CONCLUSIONS. The in vitro effects of CsA translate into a reduction in T ce lls, 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-ga mma. 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 n o change in IL-4 expression, suggesting minimal effects on type I hypersens itivity responses. There was no significant reduction in mast cell or eosin ophil 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 c hanges in conjunctival immune cell profiles.