tacrolimus and Eye-Infections--Fungal

To investigate the expression and roles of type I and II interferons (IFNs) in fungal keratitis, as well as the therapeutic effects of tacrolimus (FK506) and voriconazole on this condition.. After zymosan stimulation of mouse neutrophils, lymphocytes, macrophages, and A6(1) cells, the IFN mRNA and protein expression levels were markedly increased until 24 h, peaking at 8 h (p<0.001). The mRNA and protein expression levels of inflammatory cytokines (IL-1α, IL-6, IL-12, and IL-17) were also upregulated after zymosan stimulation. Moreover, type I (IFN-α/β) and type II (IFN-γ) IFN expression levels were increased and positively correlated with the progression of fungal keratitis in vivo. FK506 administered with voriconazole reduced the pathological infiltration of inflammatory cells into the cornea and downregulated the expression levels of IFNs and related inflammatory cytokines.. In conclusion, this study demonstrated that type I and II IFN levels were markedly increased in fungal keratitis and that FK506 combined with voriconazole decreased the severity of fungal keratitis by suppressing type I and II IFNs and their related inflammatory responses.

Topics: Animals; Antifungal Agents; Aspergillosis; Aspergillus fumigatus; Cornea; Disease Models, Animal; Drug Combinations; Drug Synergism; Epithelial Cells; Eye Infections, Fungal; Female; Gene Expression Regulation; Interferons; Interleukins; Keratitis; Lymphocytes; Macrophages; Mice; Mice, Inbred C57BL; Neutrophils; Severity of Illness Index; Tacrolimus; Voriconazole; Zymosan

Topics: Adult; Cyclosporine; Eye Infections, Fungal; Female; Glucocorticoids; Graft Rejection; Humans; Immunosuppressive Agents; Intraocular Pressure; Keratitis; Keratoplasty, Penetrating; Male; Middle Aged; Ophthalmic Solutions; Postoperative Period; Recurrence; Retrospective Studies; Risk Factors; Tacrolimus; Treatment Outcome

To establish polyhexamethylene biguanide (PHMB) as an effective treatment for Aspergillus keratitis in a novel murine model. To determine the ability of the calcineurin inhibitors tacrolimus (FK506) and cyclosporine A (CSA) to enhance the activity of PHMB, amphotericin B (AMB), and voriconazole (VCZ) against Aspergillus keratitis.. Broth antifungal susceptibility tests were performed with PHMB, AMB, VCZ, and FK506, individually and in combination against Aspergillus fumigatus. Minimum inhibitory concentrations (MIC) and fractional inhibitory concentration index (FICI) values were used to analyze antifungal activity. In vivo studies: A novel murine model was created to establish Aspergillus keratitis. Infected mice were randomly assigned to treatment groups receiving saline, CSA, AMB, VCZ, PHMB, AMB+CSA, VCZ+CSA, or PHMB+CSA. An ophthalmologist blinded to the treatment groups assessed disease severity daily based on a grading scale. The mean end change in disease score was compared between groups.. FK506 in combination with PHMB, VCZ, or AMB enhanced fungal growth inhibition. FICI values showed an additive effect between FK506 and PHMB, AMB, or VCZ. PHMB monotherapy eliminated Aspergillus growth starting at 4 μg/mL. In vivo studies: All treatment groups showed a significant improvement in disease score compared to the control group. CSA significantly worsened VCZ activity against Aspergillus keratitis.. PHMB is an effective inhibitor of Aspergillus growth. Further investigation of the role of calcineurin inhibitors in the treatment for Aspergillus keratitis is warranted.

Topics: Amphotericin B; Animals; Aspergillosis; Aspergillus fumigatus; Biguanides; Calcineurin Inhibitors; Corneal Ulcer; Cyclosporine; Disinfectants; Drug Synergism; Eye Infections, Fungal; Immunosuppressive Agents; Male; Mice; Mice, Inbred BALB C; Microbial Sensitivity Tests; Prospective Studies; Pyrimidines; Tacrolimus; Triazoles; Voriconazole