Cellular immunity in dogs with keratoconjunctivitis sicca before and after treatment with topical 2% cyclosporine

Gilger, Brian C.; Andrews, Janice M.; Wilkie, David A.; Wyman, Milton; Lairmore, Michael Dale

doi:10.1016/0165-2427(95)05471-5

Cited by 27 publications

(34 citation statements)

References 15 publications

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“…Many human studies include flow cytometric analysis of T‐cell cytokine and surface molecule expression as biomarkers when investigating the immunosuppressive effects of drugs such as cyclosporine . Few such studies are found in the veterinary literature, though one study did demonstrate suppression of lymphocyte proliferation via flow cytometry after the use of topical cyclosporine for the treatment of keratoconjunctivitis sicca in dogs . Cytokine analysis in veterinary immunosuppression research more commonly utilizes quantitative reverse transcriptase polymerase chain reaction (QRT‐PCR) assays to measure cellular messenger ribonucleic acid (mRNA) expression .…”

Section: Discussionmentioning

confidence: 99%

Pharmacodynamic Monitoring of CanineT‐Cell Cytokine Responses to Oral Cyclosporine

Archer

Fellman

Stokes

et al. 2011

Veterinary Internal Medicne

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Background: Pharmacodynamic assays measure the immunosuppressive effects of cyclosporine on T-cells and offer an alternative assessment of efficacy in individual patients.Objective: To assess the immunosuppressive effects of high and low dosage cyclosporine on canine T-cells and to develop a novel testing system for individualized dose adjustment.Animals: Seven healthy female Walker hounds. Methods: Experimental study using a paired comparison design. Flow cytometry was used to measure T-cell expression of IL-2, IL-4, and IFN-c. Cytokine expression 8 days after oral administration of high and low dosages of cyclosporine was compared to baseline and washout values, respectively. The high dosage was initially 10 mg/kg q12h and was then adjusted to attain established immunosuppressive trough blood drug concentrations (>600 ng/mL). The low dosage was 5 mg/kg q24h.Results: High dosage cyclosporine resulted in significant decreases in IL-2 and IFN-c expression (P = .0156, P = .0156), but not IL-4 expression (P = .2188). Low dosage cyclosporine was associated with a significant decrease in IFN-c expression (P = .0156), while IL-2 expression was not affected (P = .1094).Conclusions and Clinical Importance: T-cell function is suppressed at trough blood drug concentrations exceeding 600 ng/mL, and is at least partially suppressed in some dogs at low dosages. Direct evaluation of T-cell function could be an effective, more sensitive alternative to measuring blood drug concentrations for monitoring immunosuppressive therapy.

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Section: Discussionmentioning

confidence: 99%

Pharmacodynamic Monitoring of CanineT‐Cell Cytokine Responses to Oral Cyclosporine

Archer

Fellman

Stokes

et al. 2011

Veterinary Internal Medicne

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“…In addition to increasing tear production by inhibiting T-helper lymphocyte proliferation and infiltration of lacrimal gland acini, CsA restores conjunctival goblet cell mucin production [12, 13, 17, 18]. Previous studies have shown that dogs treated with ophthalmic CsA treatment have a decreased lymphocyte stimulation index compared to control dogs and that there are measurable levels of CsA in peripheral blood of treated dogs [20, 21]. However, a more recent study did not show a change in the lymphocyte stimulation index or significant blood levels with use of topical cyclosporine [22].…”

Section: Introductionmentioning

confidence: 99%

An Investigation Comparing the Efficacy of Topical Ocular Application of Tacrolimus and Cyclosporine in Dogs

Hendrix

Ward

Stuffle

et al. 2011

Veterinary Medicine International

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The purpose of this paper was to determine the efficacy and safety of topical tacrolimus, compared to cyclosporine, for treating keratoconjunctivitis sicca (KCS) in dogs. This study was a two-phase, randomized, controlled, masked clinical trial. Phase 1 evaluated ophthalmic 0.03% tacrolimus in normal dogs. Ocular examinations were performed daily. Phase 2 evaluated the efficacy of tacrolimus in treating KCS. Half the dogs received 2% cyclosporine A; the others received 0.03% tacrolimus, both diluted in olive oil. Four ophthalmic examinations were done over 12 weeks. There was no significant difference between groups in phase I. In phase 2, there was no significant difference in Schirmer tear test I (STT) results between the two groups, and both groups had a significant increase in STT over time. Both drugs were effective in increasing the STT in dogs naïve to lacrimostimulants. Tacrolimus was effective in increasing the STT in 4 dogs currently nonresponsive to cyclosporine.

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“…We evaluated changes in T‐lymphocyte subsets (CD4/CD8) and proliferation of peripheral blood lymphocytes, and found that dogs with KCS had normal lymphocyte proliferation prior to the initiation of treatment. However, after 3 months of topical 2% CsA treatment, there was a significant decrease in the stimulation index (measure of proliferation compared to untreated lymphocytes) 38 . The CD4:CD8 lymphocyte ratios were unchanged.…”

Section: Current Uses Of Csa In Veterinary Ophthalmologymentioning

confidence: 90%

“…No attempts were made to measure the systemic absorption of the medication or the effect on peripheral blood T lymphocytes. To determine whether topical administration of CsA had any systemic effect or whether there were blood levels achievable from topical application, we evaluated 10 dogs with KCS beginning before, and after 1 and 3 months of administration of 2% CsA into each eye twice daily 38 . We evaluated changes in T‐lymphocyte subsets (CD4/CD8) and proliferation of peripheral blood lymphocytes, and found that dogs with KCS had normal lymphocyte proliferation prior to the initiation of treatment.…”

Section: Current Uses Of Csa In Veterinary Ophthalmologymentioning

confidence: 99%

Cyclosporine A in veterinary ophthalmology

Gilger

Allen

1998

Veterinary Ophthalmology

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Cellular immunity in dogs with keratoconjunctivitis sicca before and after treatment with topical 2% cyclosporine

Cited by 27 publications

References 15 publications

Pharmacodynamic Monitoring of CanineT‐Cell Cytokine Responses to Oral Cyclosporine

Pharmacodynamic Monitoring of CanineT‐Cell Cytokine Responses to Oral Cyclosporine

An Investigation Comparing the Efficacy of Topical Ocular Application of Tacrolimus and Cyclosporine in Dogs

Cyclosporine A in veterinary ophthalmology

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