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Title: Pimecrolimus 1% cream for the treatment of discoid lupus erythematosus
Author: Navarro-Partida, J.
Martinez-Rizo, A.B.
Gonzalez-Cuevas, J.
Arrevillaga-Boni, G.
Ortiz-Navarrete, V.
Armendariz-Borunda, J.
Issue Date: 2012
Abstract: Polarized T helper type 2 (Th2) response is linked with fibrosis. Here, we evaluated the effect of the anti-fibrotic agent pirfenidone on Th type 1 (Th1) and Th2 responses. For in vivo testing; Wistar rats were made cirrhotic by intraperitoneal administration of thioacetamide. Once hepatic damage was established, pirfenidone was administered intragastrically on a daily basis during three weeks. Gene expression of Th marks was evaluated by RT-PCR and Western blot assays from liver homogenates. Pirfenidone therapy induced down-regulation of Th2 transcripts and proteins (GATA3 and IL-4), without affecting significantly Th1 genes expression (T-bet and IFN-?). We found that the activated form of p38 MAPK (identified by Western blot) was reduced by pirfenidone treatment, which is consistent with the anti-Th2 activity observed. Pirfenidone reduced GATA3 nuclear localization without modifying its DNA binding activity (evaluated by electrophoretic mobility shift assay). For in vitro testing; human naive CD4+ T cells were cultured in either Th1 or Th2 polarizing conditions in the presence of pirfenidone and flow cytometric analysis of intracellular synthesis of IFN-? and IL-4 was conducted. Pirfenidone impaired development of Th2 subpopulation. In conclusion, pirfenidone is capable of impairing Th2 differentiation and limits Th2 profibrogenic response. The mechanism involves p38 inhibition and regulation of GATA3 expression and translocation. " 2011 Elsevier B.V. All rights reserved.",,,,,,"10.1016/j.ejphar.2011.12.025",,,"","",,,,,,"01-mar",,"European Journal of Pharmacology",,"71
WOS",,,,"Index Medicus;Animals;Anti-Inflammatory Agents, Non-Steroidal/pd [Pharmacology];Anti-Inflammatory Agents, Non-Steroidal/tu [Therapeutic Use];Cell Differentiation/de [Drug Effects];Cell Differentiation/ge [Genetics];Cells, Cultured;Collagen Type I/me [Metabolism];DNA/me [Metabolism];Down-Regulation/de [Drug Effects];Drug Evaluation, Preclinical/mt [Methods];GATA3 Transcription Factor/me [Metabolism];Gene Expression;Interferon-gamma;Interleukin-4/me [Metabolism];Liver/me [Metabolism];Liver/pa [Pathology];Liver Cirrhosis, Experimental/dt [Drug Therapy];Liver Cirrhosis, Experimental/me [Metabolism];Liver Cirrhosis, Experimental/pa [Pathology];Male;Pyridones/pd [Pharmacology];Pyridones/tu [Therapeutic Use];Rats;Rats, Wistar;T-Box Domain Proteins/me [Metabolism];Th1 Cells/cy [Cytology];Th1 Cells/de [Drug Effects];Th1 Cells/me [Metabolism];Th2 Cells/cy [Cytology];Th2 Cells/de [Drug Effects];Th2 Cells/me [Metabolism];p38 Mitogen-Activated Protein Kinases/me [Metabolism]",,"Immunomodulation; Liver fibrosis; Pirfenidone; T helper response",,,,,,"Pirfenidone restricts Th2 differentiation in vitro and limits Th2 response in experimental liver fibrosis",,"Article" "45409","123456789/35008",,"Tlacuilo-Parra, A., Medical Research Division, Instituto Mexicano del Seguro Social, Universidad de Colima, Guadalajara, Jalisco, Mexico, Monte Olimpo 1413, Guadalajara, Jalisco, Mexico; Guevara-Gutiérrez, E., Dermatology Department, Instituto Dermatológico de Jalisco, Zapopan, Jalisco, Mexico; Gutiérrez-Murillo, F., Dermatology Department, Instituto Dermatológico de Jalisco, Zapopan, Jalisco, Mexico; Soto-Ortiz, A., Dermatology Department, Instituto Dermatológico de Jalisco, Zapopan, Jalisco, Mexico; Barba-Gómez, F., Dermatology Department, Instituto Dermatológico de Jalisco, Zapopan, Jalisco, Mexico; Hernández-Torres, M., Dermatology Department, Instituto Dermatológico de Jalisco, Zapopan, Jalisco, Mexico; Salazar-Páramo, M., Medical Research Division, Instituto Mexicano del Seguro Social and CUCS, Universidad de Guadalajara, Guadalajara, Jalisco, Mexico",,"Tlacuilo-Parra, A.
Guevara-Gutierrez, E.
Gutierrez-Murillo, F.
Soto-Ortiz, A.
Barba-Gomez, F.
Hernandez-Torres, M.
Salazar-Paramo, M.",,"2005",,"Objectives. To determine the safety and efficacy of pimecrolimus cream on lesions of discoid lupus erythematosus. Methods. In an open-label phase II trial, patients with discoid lupus were treated with pimecrolimus 1% cream twice daily for 8 weeks. We assessed skin involvement with a clinical severity score, quality of life, patient improvement and toxicity. The changes were documented by skin biopsy at baseline and at the end of treatment. Results. Ten patients with a mean age of 34 17 yr and disease duration of 3 yr (range 1-8) were studied; 90% were female and 40% had received prior topical or systemic therapy without response. In all patients, improvement of skin damage was observed after therapy. A significant decrease of 52% was observed in the mean S.D. clinical severity score, from 6.1 1.4 before treatment to 2.9 1.5 after treatment (P = 0.005). Quality of life score (0 = no effect, 100 = maximum effect on quality of life) showed a mean improvement of 46%, from 42.8 23.1 before to 23 16.5 after treatment (P = 0.008). According to the patients' assessment of the response to treatment, 50% qualified as marked improvement, 40% moderate and 10% slight improvement. The treatment was well tolerated; adverse reactions consisted of minimal erythema and pruritus, which resolved without any further action. Conclusions. Our data suggest that pimecrolimus cream for discoid lupus erythematosus seems to be a safe and clinically effective option. However, this was an open and uncontrolled study, and double-blind, placebo-controlled studies are needed. " The Author 2005. Published by Oxford University Press on behalf of the British Society for Rheumatology. All rights reserved.
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