Immunomodulatory effects of tacrolimus (FK506) for the treatment of allergic diseases

Kandikattu, Hemanth Kumar; Mishra, Anil

doi:10.5281/zenodo.2530969

2018

DOI: 10.5281/zenodo.2530969

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Immunomodulatory effects of tacrolimus (FK506) for the treatment of allergic diseases

Hemanth Kumar Kandikattu

Anil Mishra

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Cited by 3 publications

References 33 publications

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Tacrolimus (FK506) treatment protects allergen‐, IL‐5‐ and IL‐13‐induced mucosal eosinophilia

et al. 2021

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Eosinophils are a common clinical feature associated with chronic allergic diseases, and elemental diets, systemic steroids, anti-IL-5 and anti-IL-13 treatment have shown some therapeutic promise. Herein, we present evidence that pre-and post-intraperitoneal administration of tacrolimus (FK506) is very effective in reducing CCR3/Siglec-F + eosinophils in Aspergillus-challenged asthma and EoE, CD2-IL-5 induced global eosinophilia, and DOX regulated IL-13-induced asthma. We used flow cytometry and anti-major basic protein (MBP) immunostaining to examine eosinophils in the spleen, bone marrow, BALF, lung, oesophagus and intestine. Additionally, we also performed ELISA and Western blot analyses to show that tacrolimus treatment also reduces the levels of eosinophil-specific cytokines IL-4, IL-5, IL-13 and TGF-b, eosinophil-specific chemokines Eotaxin-1 and Eotaxin-2, and progenitors of target RCAN1 mRNA and protein levels. Additionally, the current investigations also show that the TGF-bmediated oesophageal and lung fibrosis is also reduced in Aspergilluschallenged, CD2-IL-5 transgenic and DOX-responsive IL-13 mice. Mechanistically, we show that tacrolimus in vitro treatment inhibited bone marrow-derived eosinophil proliferation and viability by promoting eosinophil apoptosis that may be associated with downregulation of RCAN1. Taken together, we provide in vivo and in vitro evidence that tacrolimus ameliorates eosinophil levels and associated pathogenesis in allergen-, IL-5-and IL-13-induced EoE, EG and asthma pathogenesis. Considering tacrolimus side-effects and reactivity to several other drugs, we propose the topical use of tacrolimus for paediatric and low-dose oral for adult patients as a novel therapeutic strategy for the clinical trial to reduce mucosal eosinophilia first in steroid-refractory or elemental diet non-responsive adult EoE, EG and asthma patients.

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Tacrolimus (FK506) treatment protects allergen‐, IL‐5‐ and IL‐13‐induced mucosal eosinophilia

et al. 2021

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Efficacy and safety of tacrolimus-based treatment for non-rapidly progressive IgA nephropathy

Zhao

Yue

et al. 2023

Front. Pharmacol.

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In this study, we aimed to evaluate the efficacy and safety of tacrolimus-based treatment for immunoglobulin A nephropathy (IgAN). We retrospectively reviewed 127 adult patients with primary IgAN with 24 h urine total protein quantity (24 h UTP) ≥ 1 g and serum creatinine ≤3 mg/dL. All patients were divided into tacrolimus (TAC) and control (non-TAC) groups according to the treatment strategy. Proteinuria remission, remission rate, and adverse events were compared between the two groups. Among the 127 patients, 61 received TAC-based treatment and 66 received non-TAC treatment. TAC group exhibited a more rapid decline in proteinuria than the non-TAC group at 3, 9, and 12 months (p = 0.049, 0.001, and 0.018, respectively). Remission rates at 1, 3, 6, 9, and 12 months were 41.0, 68.9, 80.3, 90.2, and 88.5%, respectively, in the TAC group. These rates were higher than those in the control group at 3, 9, and 12 months (p = 0.030, 0.008, and 0.026, respectively). Complete remission rates at 1, 3, 6, 9, and 12 months were 6.56, 19.7, 37.7, 54.1, and 62.3%, respectively, in the TAC group. These rates were higher than those in the control group at 9 and 12 months (p = 0.013 and 0.008, respectively). The estimated mean time to complete remission was significantly shorter in the TAC group than in the control group (p = 0.028). TAC did not increase the incidence of adverse events. In conclusion, TAC accelerated proteinuria remission in patients with non-rapidly progressive IgAN with no increased risk of adverse events. Further prospective randomized controlled trials are necessary to validate our findings.

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Characterization and In Vitro and In Vivo Evaluation of Tacrolimus-Loaded Poly(ε-Caprolactone) Nanocapsules for the Management of Atopic Dermatitis

et al. 2021

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Background: Tacrolimus (TAC) is a drug of natural origin used in conventional topical dosage forms to control atopic dermatitis. However, direct application of the drug often causes adverse side effects in some patients. Hence, drug nanoencapsulation could be used as an improved novel therapy to mitigate the adverse effects and enhance bioavailability of the drug. Methods: Physicochemical properties, in vitro drug release experiments, and in vivo anti-inflammatory activity studies were performed. Results: TAC-loaded nanocapsules were successfully prepared by the interfacial deposition of preformed polymer using poly(ε-caprolactone) (PCL). The nanoparticulate systems presented a spherical shape with a smooth and regular surface, adequate diameter (226 to 250 nm), polydispersity index below 0.3, and suitable electrical stability (−38 to −42 mV). X-ray diffraction confirmed that the encapsulation method provided mainly the drug molecular dispersion in the nanocapsule oily core. Fourier-transform infrared spectra suggested that nanoencapsulation did not result in chemical bonds between drug and polymer. In vitro drug dissolution experiments showed a controlled release with a slight initial burst. The release kinetics showed zero-order kinetics. As per the Korsmeyer–Peppas model, anomalous transport features were observed. TAC-loaded PCL nanocapsules exhibited excellent anti-inflammatory activity when compared to the free drug. Conclusions: TAC-loaded PCL nanocapsules can be suitably used as a novel nano-based dosage form to control atopic dermatitis.

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Immunomodulatory effects of tacrolimus (FK506) for the treatment of allergic diseases

Cited by 3 publications

References 33 publications

Tacrolimus (FK506) treatment protects allergen‐, IL‐5‐ and IL‐13‐induced mucosal eosinophilia

Tacrolimus (FK506) treatment protects allergen‐, IL‐5‐ and IL‐13‐induced mucosal eosinophilia

Efficacy and safety of tacrolimus-based treatment for non-rapidly progressive IgA nephropathy

Characterization and In Vitro and In Vivo Evaluation of Tacrolimus-Loaded Poly(ε-Caprolactone) Nanocapsules for the Management of Atopic Dermatitis

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