RESUMO
OBJECTIVE: To investigate the effects of secukinumab treatment for psoriasis on different functional cytokines and inflammatory mediators in patients' serum METHODS: Enzyme-linked immunosorbent assay was used to detect interleukin (IL)-1ß and IL-1RA associated with intrinsic immunity; IL-6, IL-18, and growth regulated oncogene alpha (GROα) associated with neutrophils; IL-12, tumour necrosis factor (TNF)-α, and interferon (IFN)-γ associated with Th1; IL-23, IL-17A, and IL-22 associated with Th17; Thymus activation regulated chemokine (TARC), IL-13, and defensin beta 2 (DEFB2) associated with Th2; Vascular endothelial growth factor (VEGF)-A and IL-10 associated with angiogenesis; and IFN-γ associated with sepsis in the peripheral blood of 12 patients with common psoriasis treated with secukinumab and 15 healthy controls. IL-23, IL-17A, IL-22 associated with Th17; TARC, IL-13, DEFB2 associated with Th2; VEGF-A, IL-10 associated with angiogenesis and procalcitonin (PCT) associated with sepsis. The differences in expression of the above cytokines before and after treatment and the correlation with psoriasis disease severityï¼»Psoriasis Area Severity Index(PASI) scoreï¼½, age, and disease duration were analyzed. RESULTS: The mean PASI score of the enrolled patients with moderate to severe psoriasis was 21.6 ± 11.0 before treatment and decreased to below 1 after treatment. Serum IL-6; IL-18, GROα, IFN-γ, TNF-α, VEGF-A, and IL-17A were significantly higher than normal. And IL-17A and IFN-γ were positively correlated with disease duration and age, and IL-18 was positively correlated with PASI score. The expression levels of IL-6, GROα, VEGF-A, IFN-γ, TNF-α, IL-17A and IL-23 were significantly lower after secukinumab treatment compared with those before treatment, but the expression levels of IFN-γ, VEGF-A, TARC, IL-13, and DEFB2 were still significantly higher than those of normal subjects after treatment CONCLUSIONS: secukinumab clears skin lesions by antagonizing IL-17A and simultaneously decreasing the expression levels of IL-6, GRO α, VEGF-A, IFN-γ, TNF-α, IL-17A, and IL-23.
RESUMO
BACKGROUND: Hypophosphatemic osteomalacia (HO) is an unusual metabolic disease characterized by low concentrations of serum phosphate levels, which leads to reduced mineralization of the bone matrix. Typically, HO consists of 4 common types: X-linked dominant hypophosphatemia (XLH), autosomal dominant hypophosphatemic rickets (ADHR), tumor-induced osteomalacia (TIO), and sporadic HO. CASE PRESENTATION: We herein report the case of a 48-year-old man who developed multiple joint and bone pain and muscle weakness over 5 months with a 23-year history of psoriasis. He was diagnosed with psoriatic arthritis by primary hospitals but was unresponsive to etanercept and adalimumab treatments. After referral to our hospital, the patient was diagnosed with HOs combined with psoriasis. The patient was treated with oral phosphate solution, calcium, and active vitamin D, and the symptoms of bone and joint pain and muscle weakness gradually relieved. Since TIO accounts for the majority of adult-onset HO, positron emission tomography - computed tomography or octreotide imaging examinations had been done yearly to locate any underlying tumor in our patient, with negative findings in the 4-year follow-up. CONCLUSIONS: Diagnosis of HO remains a challenge to rheumatologists, and especially to dermatologists when accompanied by psoriasis. After excluding the inherited HO and with negative tumor, this report may be the first male case of sporadic HO combined with psoriasis.
Assuntos
Hipofosfatemia , Neoplasias , Osteomalacia , Psoríase , Adulto , Humanos , Masculino , Pessoa de Meia-Idade , Osteomalacia/etiologia , Hipofosfatemia/diagnóstico , Hipofosfatemia/etiologia , Hipofosfatemia/metabolismo , Fosfatos/metabolismo , Neoplasias/complicações , Psoríase/complicaçõesAssuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Linfócitos T CD4-Positivos/patologia , Neoplasias Palpebrais/patologia , Linfoma Cutâneo de Células T/patologia , Recidiva Local de Neoplasia , Neoplasias Cutâneas/patologia , Adulto , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Linfócitos T CD4-Positivos/efeitos dos fármacos , Neoplasias Palpebrais/tratamento farmacológico , Humanos , Interferon-alfa/administração & dosagem , Linfoma Cutâneo de Células T/tratamento farmacológico , Masculino , Metotrexato/administração & dosagem , Prednisona/administração & dosagem , Neoplasias Cutâneas/tratamento farmacológicoRESUMO
It is currently believed that psoriasis and allergic contact dermatitis (ACD) are different diseases; however, they share clinical similarities. The involvement of T helper 17 (Th17) cells in these disorders provides a novel opportunity to investigate the relationship between them. The present study aimed to determine whether the same or overlapping inflammatory pathways are involved in the two diseases, and the influence of different types of ACD on psoriasis. Compound mouse models of Th1 or Th2type contact hypersensitivity (CHS) combined with imiquimod (IMQ)induced psoriasislike inflammation were established, in order to mimic the characteristics of ACD and psoriasis. Histopathology, immunohistochemistry and cytokine detection in blood serum and tissues were used to compare the differences between the mice treated with IMQ alone or IMQ combined with Th1 and Th2type CHS. As compared with the IMQtreated mice or IMQ-treated Th1type CHS mice, the mice with Th2type CHS treated with IMQ exhibited more serious psoriasislike inflammation with increased epidermal thickness and infiltrating cells in the derma. High mRNA expression levels of interleukin (IL)17, IL22, IL23, TNFα and RORγt were detected in back skin lesions. Additionally, high levels of IL17 and IL22 in blood serum were detected in IMQtreated mice combined with Th2type CHS. The mice treated with IMQ alone, and IMQ treatment combined with Th1type CHS had a comparable psoriasislike inflammatory response in the back skin. In conclusion, these data demonstrate that Th2type CHS exacerbated the IMQtreated psoriatic inflammation of mice via the IL23/IL17 axis. Th17 cells and associated pathways may link ACD and psoriasis. Therefore, patients with psoriasis should avoid contact with specific sensitizers, such as fragrance and rubber products, which may induce Th2 polarization.
Assuntos
Aminoquinolinas/efeitos adversos , Dermatite de Contato/complicações , Dermatite de Contato/imunologia , Psoríase/etiologia , Psoríase/patologia , Animais , Biomarcadores , Citocinas/sangue , Citocinas/genética , Citocinas/metabolismo , Modelos Animais de Doenças , Feminino , Expressão Gênica , Imiquimode , Camundongos , Psoríase/metabolismo , Pele/imunologia , Pele/metabolismo , Pele/patologia , Células Th1/imunologia , Células Th1/metabolismo , Células Th17/imunologia , Células Th17/metabolismo , Células Th2/imunologia , Células Th2/metabolismoRESUMO
Psoriasis is a T cell-mediated, chronic, relapsing and inflammatory cutaneous disorder. The dysfunctional activity of T cells in patients with psoriasis is attributed to bone marrow hematopoietic stem cells (BMHSCs). To understand the pathogenic roles of BMHSCs in psoriasis, a differential gene expression analysis was performed using suppression subtractive hybridization of the BMHSCs from a patient with psoriasis and a healthy control. Using a cDNA array dot blot screening to screen 600 genes from forward- and reverse-subtracted cDNA libraries, 17 differentially-expressed sequence tags (ESTs) were identified. The genes within the ESTs were observed to be the homologs of genes that are involved in various cellular processes, including hormone signaling, RNA catabolism, protein ADP DNA base melting, transcriptional regulation, cell cycle regulation and metabolism. CD45, which was overexpressed in the psoriatic BMHSCs, was further analyzed using relative quantitative polymerase chain reaction. In addition, the levels of CD45 in the peripheral blood cells (PBCs) of the patients with psoriasis were markedly increased and closely associated with disease severity. An abnormality of hematopoietic progenitor cells, e.g., CD45 overexpression, may be transferred to PBCs via hematopoiesis, and may account for the psoriasis-inducing properties of activated T cells.
Assuntos
Células da Medula Óssea/citologia , Células-Tronco Hematopoéticas/metabolismo , Psoríase/genética , Técnicas de Hibridização Subtrativa , Adulto , Células Cultivadas , Etiquetas de Sequências Expressas , Feminino , Biblioteca Gênica , Células-Tronco Hematopoéticas/citologia , Humanos , Antígenos Comuns de Leucócito/genética , Antígenos Comuns de Leucócito/metabolismo , Masculino , Pessoa de Meia-Idade , Análise de Sequência com Séries de Oligonucleotídeos , Psoríase/metabolismo , Psoríase/patologia , RNA Mensageiro/metabolismo , Índice de Gravidade de DoençaRESUMO
Camptothecin is a topoisomerase I inhibitor with definite anti-psoriatic effect. As it is limited in clinical application because of serious side effects and toxicity, many researchers are striving hard to develop derivatives or analogues of camptothecin with higher effects and less toxicity. To explore the anti-psoriatic potential of isocamptothecin, a novel camptothecin analogue, its effects on proliferation, apoptosis and telomerase activity were investigated in the human keratinocyte cell line HaCaT. Incubation with isocamptothecin resulted in a time- and concentration-dependent inhibition of HaCaT cell proliferation. However, isocamptothecin showed larger inhibitory concentration at 50% than camptothecin, suggesting far less cytotoxicity. In addition, isocamptothecin induced apoptosis in a concentration-dependent manner and induced typical morphologic features of apoptosis in HaCaT cells. Moreover, isocamptothecin downregulated the telomerase activity of HaCaT cells not only at concentrations of apoptosis induction but also at concentration insufficient to induce apoptosis, providing additional mechanisms that further account for its ability to inhibit keratinocytes proliferation and induce apoptosis. These results indicate that isocamptothecin possesses similar effects on keratinocytes with camptothecin, but shows far less cytotoxicity, it may probably become a promising agent for psoriasis therapy.