Interleukin-6 levels in the conjunctival epithelium of patients with dry eye disease treated with cyclosporine ophthalmic emulsion.
OBJECTIVE
To evaluate interleukin-6 (IL-6) levels in the conjunctival epithelium of patients with moderate to severe dry eye disease before and after treatment with cyclosporin A ophthalmic emulsion (CsA) or its vehicle.


METHODS
Conjunctival cytology specimens were obtained from a subset of patients enrolled in a 6-month randomized, double-masked clinical trial of the efficacy and safety of topical CsA at baseline and after 3 and 6 months of B.I.D. treatment with 0.05% cyclosporine emulsion (n = 13), 0.1% cyclosporine emulsion (n = 8), or vehicle (n = 10). RNA was extracted and a competitive reverse transcriptase polymerase chain reaction (RT-PCR) was used to evaluate the levels of mRNA encoding the inflammatory cytokine IL-6 and a housekeeping gene, G3PDH. Levels of IL-6 and G3PDH were measured and compared.


RESULTS
There was no change from baseline in the level of G3PDH after 3 or 6 months in any group. IL-6 normalized for G3PDH (IL-6/G3PDH ratio) was not different from baseline at 3 months but showed a significant decrease from baseline in the group treated with 0.05% CsA (p = 0.048) at 6 months. No significant between-group differences were noted and no correlation was observed between the change in IL-6/G3PDH and corneal fluorescein staining.


CONCLUSIONS
This preliminary, small-cohort study showed a decrease in IL-6 in the conjunctival epithelium of moderate to severe dry eye patients treated with 0.05% CsA for 6 months. The observed decrease suggests that dry eye disease involves immune-mediated inflammatory processes that may be decreased by treatment with topical ophthalmic cyclosporine.
Turner
K
K
Bascom Palmer Eye Institute, Department of Ophthalmology, University of Miami School of Medicine, Florida 33136, USA.
Pflugfelder
S C
SC
Ji
Z
Z
Feuer
W J
WJ
Stern
M
M
Reis
B L
BL
D000287:Administration, Topical; D015415:Biomarkers; D003228:Conjunctiva / Q000378:metabolism* / Q000473:pathology; D016572:Cyclosporine / Q000627:therapeutic use*; D017931:DNA Primers / Q000737:chemistry; D004311:Double-Blind Method; D015352:Dry Eye Syndromes / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D004655:Emulsions; D004848:Epithelium / Q000378:metabolism* / Q000473:pathology; D005987:Glyceraldehyde-3-Phosphate Dehydrogenases / Q000378:metabolism; D006801:Humans; D007166:Immunosuppressive Agents / Q000627:therapeutic use*; D015850:Interleukin-6 / Q000235:genetics / Q000378:metabolism*; D011446:Prospective Studies; D012333:RNA, Messenger / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction
D015415:Biomarkers; D017931:DNA Primers; D004655:Emulsions; D007166:Immunosuppressive Agents; D015850:Interleukin-6; D012333:RNA, Messenger; D016572:Cyclosporine; D005987:Glyceraldehyde-3-Phosphate Dehydrogenases