Statin effects on regulatory and proinflammatory factors in chronic idiopathic urticaria

Autor(es)

Azor, M. H. ^[1] ; dos Santos, J. C. ^[1] ; Futata, E. A. ^[1] ; de Brito, C. A. ^[1] ; Maruta, C. W. ^[2] ; Rivitti, E. A. ^[2] ; da Silva Duarte, A. J. ^[1] ; Sato, M. N. ^[1]

Afiliação do(s) autor(es)

^[1] Univ Sao Paulo, Sch Med, Hosp Clin, Lab Dermatol & Immunodeficiencies LIM 56, Dept Der, BR-05403000 Sao Paulo - Brazil

^[2] Univ Sao Paulo, Sch Med, Hosp Clin, Dermatol Outpatient Clin, BR-05403000 Sao Paulo - Brazil

• Tipo de documento: Artigo Científico
• Fonte: CLINICAL AND EXPERIMENTAL IMMUNOLOGY; v. 166, n. 2, p. 291-298, NOV 2011.
• Citações Web of Science: 20

Resumo

Immunological dysfunction has been described to occur in chronic idiopathic urticaria (CIU), most notably in association with an inflammatory process. Some pharmacological agents as statins - drugs used in hypercholesterolaemia - display a broad effect on the immune response and thus should be tested in vitro in CIU. Our main objectives were to evaluate the effects of statins on the innate and adaptive immune response in CIU. Simvastatin or lovastatin have markedly inhibited the peripheral blood mononuclear cells (PBMC) proliferative response induced by T and B cell mitogens, superantigen or recall antigen. Simvastatin arrested phytohaemaglutinin (PHA)induced T cells at the G0/G1 phase, inhibiting T helper type 1 (Th1), Th2, interleukin (IL)-10 and IL-17A cytokine secretion in both patients and healthy control groups. Up-regulation of suppressor of cytokine signalling 3 (SOCS3) mRNA expression in PHA-stimulated PBMCs from CIU patients was not modified by simvastatin, in contrast to the enhancing effect in the control group. Statin exhibited a less efficient inhibition effect on cytokine production {[} IL-6 and macrophage inflammatory protein (MIP)-1 alpha] induced by Toll-like receptor (TLR)-4, to which a statin preincubation step was required. Furthermore, statin did not affect the tumour necrosis factor (TNF)-alpha secretion by lipopolysaccharide (LPS)-stimulated PBMC or CD14(+) cells in CIU patients. In addition, LPS-activated PBMC from CIU patients showed impaired indoleamine 2,3-dioxygenase (IDO) mRNA expression compared to healthy control, which remained at decreased levels with statin treatment. Statins exhibited a marked down-regulatory effect in T cell functions, but were not able to control TLR-4 activation in CIU patients. The unbalanced regulatory SOCS3 and IDO expressions in CIU may contribute to the pathogenesis of the disease. (AU)

• Processo FAPESP: 06/53601-8 - Atividade imunorregulatoria da enzima indolamina dioxigenase e efeito in vitro da estatina e citocinas no catabolismo do triptofano na urticaria cronica autoimune.
• Beneficiário: Maria Notomi Sato
• Modalidade de apoio: Auxílio à Pesquisa - Regular
• Processo FAPESP: 06/57926-9 - Atividade imunorregulatória da enzima indolamina dioxigenase e influência da estatina em células mononucleares de pacientes com urticária crônica autoimune
• Beneficiário: Mayce Helena Azor
• Modalidade de apoio: Bolsas no Brasil - Doutorado Direto