Everolimus improves experimental autoimmune uveoretinitis

Hennig, Maren; Bauer, Dirk; Wasmuth, Susanne; Busch, Martin; Walscheid, Karoline; Thanos, Solon; Heiligenhaus, Arnd

doi:10.1016/j.exer.2012.09.003

Cited by 23 publications

(18 citation statements)

References 47 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…TARC participates in the type 2 helper T cell (Th2) immune response, and serum TARC levels are related to the activity of eczema in atopic dermatitis . It was reported that everolimus downregulated inflammation caused by Th1 cells in experimental animal models of Crohn's disease and autoimmune uveoretinitis . However, Han et al recently demonstrated that although interferon gamma mRNA levels were greatly reduced, interleukin‐4 mRNA levels increased in the everolimus‐treated splenic mononuclear cells of experimental autoimmune neuritis rats.…”

Section: Resultsmentioning

confidence: 99%

Two cases of eczematous eruptions caused by everolimus

Habu

Tohyama

Sayama

2019

J Cutaneous Imm & Allergy

View full text Add to dashboard Cite

Objective Everolimus, an inhibitor of the mammalian target of rapamycin, has been used in the treatment of several types of tumor. Erythematous maculopapular and acneiform rashes are the major dermatological adverse events associated with everolimus therapy, but we encountered two cases of eczematous eruption caused by everolimus. Method We assessed the clinical features and laboratory findings of the two cases. Results A 52‐year‐old woman and a 59‐year‐old man developed pruritic papules and erythema over their entire bodies after initiation of everolimus therapy. Both patients exhibited peripheral eosinophilia and increased serum thymus and activation‐regulated chemokine (TARC) levels. A skin biopsy from one patient revealed the features of chronic dermatitis. Both the skin manifestations and the pruritis disappeared rapidly after the discontinuation of everolimus treatment. The peripheral blood eosinophil and serum TARC levels also decreased. Conclusion Eczematous eruption associated with an elevated serum TARC level is a dermatological event associated with everolimus therapy.

show abstract

Section: Resultsmentioning

confidence: 99%

Two cases of eczematous eruptions caused by everolimus

Habu

Tohyama

Sayama

2019

J Cutaneous Imm & Allergy

View full text Add to dashboard Cite

show abstract

“…The protocol was approved by the North Rhine-Westphalia State Agency for Nature, Environment, and Consumer Protection (LANUV). All experimental procedures conformed to the guidelines of the National Institutes of Health and the Association for Research in Vision and Ophthalmology resolution on the use of animals in research [24] .…”

Section: Micementioning

confidence: 99%

“…Then, 10 μg/ mL hIRBP p161-180 peptide, monoclonal antibody (mAb) anti-CD3e (clone 145-2C11; BD Pharmingen, Hamburg, Germany), 5 μg/mL concanavalin A (ConA; Biochrom, Berlin Germany), or medium (control) was added. The supernatant of each well was harvested after 24 h and stored at -80 ° C until use [24,28] .…”

Section: Cell Culturementioning

confidence: 99%

“…A total of 200 μL emulsion was administered subcutaneously to both thighs and the base of the tail. Furthermore, 0.4 μg PTX (Sigma Aldrich) in 100 μL PBS was injected intraperitoneally [24] .…”

Section: Eau Inductionmentioning

confidence: 99%

“…Five-micrometer sections were stained with hematoxylin-eosin. Three representative sections per eye were evaluated in a masked fashion on a scale from 0 to 4, depending on the number, type, and size of lesions, as described previously [24,26,27] . EAU scores were determined 21 days after immunization with hIRBP p161-180 or 14 days after adoptive transfer [21] .…”

Section: Eau Scoring By Histologymentioning

confidence: 99%

See 2 more Smart Citations

Behavioral Conditioning of Immune Responses with Cyclosporine A in a Murine Model of Experimental Autoimmune Uveitis

Bauer

Busch²,

Pacheco-López³

et al. 2017

Neuroimmunomodulation

View full text Add to dashboard Cite

Objective: We examined the role of behavioral conditioning of immune responses with cyclosporine A (CsA) on the development of Th1/Th17-driven experimental autoimmune uveoretinitis (EAU). Methods: Mice received a 0.2% w/v saccharin solution as conditioned stimulus combined with CsA (20 mg/kg) in 6 association trials at 72-h intervals. For evocation periods, conditioned mice were reexposed to saccharin, whereas the conditioned but not reexposed group received water only. Animals were immunized with human interphotoreceptor-retinoid-binding protein peptide 161-180 (hIRBP_p161-180) peptide in complete Freund adjuvant (CFA) and a concomitant injection of pertussis toxin. Results: In naïve mice subjected to the behavioral conditioning regimen, mitogen-induced interleukin (IL)-2 production was decreased in conditioned mice compared to conditioned but not reexposed animals. Incidence and severity of EAU were not significantly lower in behaviorally conditioned and immunized mice. ELISA analysis of splenocytes revealed a reduced interferon (IFN)-γ/IL-17 ratio in CsA-treated, conditioned but not reexposed, and conditioned animals. The adoptive transfer of antigen-specific splenocytes from animals behaviorally conditioned with CsA to naïve mice decreased the severity of EAU in recipient mice compared to the control group. In vitro activation of splenocytes isolated from immunized mice with agonists targeting TLR2 and NOD2 together with β₂-adrenergic activation (induced by epinephrine, norepinephrine, or salbutamol) resulted in decreased IFN-γ but increased IL-17 immune responses. The β₂-adrenergic antagonist propranolol could restore IFN-γ production, whereas only the norepinephrine-induced increase in IL-17 production was abrogated. Conclusions: We conclude that CsA conditioning in the EAU model mitigates Th1 but enhances Th17 immune responses, and does not ameliorate disease. The results imply that in EAU the mechanism of immune conditioning interacts with CFA components during active immunization, most likely via the TLR2/NOD2 pathway, and induces differentiation of Th17 cells that drive autoimmune diseases.

show abstract

T Cell Inhibitors

Read

2019

Treatment of Non-Infectious Uveitis

View full text Add to dashboard Cite

Everolimus improves experimental autoimmune uveoretinitis

Cited by 23 publications

References 47 publications

Two cases of eczematous eruptions caused by everolimus

Two cases of eczematous eruptions caused by everolimus

Behavioral Conditioning of Immune Responses with Cyclosporine A in a Murine Model of Experimental Autoimmune Uveitis

T Cell Inhibitors

Contact Info

Product

Resources

About