Serum Concentration of Interleukin-6 Is Increased Both in Active and Remission Stages of Pemphigus Vulgaris

Lukamowicz, Jolanta; Bogaczewicz, Jarosław; Sysa-Jędrzejowska, Anna; Torzecka, Jolanta Dorota; Lesiak, Aleksandra

doi:10.1155/2008/875394

Cited by 34 publications

(25 citation statements)

References 21 publications

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“…With one exception [44], a majority of studies measured the cytokine levels in patient serum using high sensitivity ELISA. Induction of TH2 cells in the pathogenesis of pemphigus was further confirmed demonstrating increased levels of the classic TH2 cytokines, IL-4 and IL-10 [15,45], as well as increases in additionally defined TH2 cytokines, IL-5 [Sinha unpublished data] and IL-6 [1,44,46]. Interestingly, D'Auria et al while demonstrating no significant elevations for many of the TH2 cytokines (IL-4, IL-5, and IL-10), suggested not only an increase in IL-6 but demonstrated the association between the serum levels of the cytokine and the number of clinical lesions [1].…”

Section: Thmentioning

confidence: 88%

Cytokine networks in Pemphigus vulgaris: An integrated viewpoint

Giordano

Sinha

2012

Autoimmunity

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Pemphigus vulgaris (PV) is an autoimmune bullous skin disease where tolerance to the desmosomal protein desmoglein 3 (Dsg3), and perhaps additional epidermal targets, is lost, leading to the production of autoantibodies directed against cellular adhesion molecules. As auto-reactive T cells are involved in the induction and maintenance of antibody production, it has been hypothesized that cytokines play a crucial role in disease pathogenesis. Qualitative and quantitative alterations in cytokine profiles have been previously reported; however, despite recent advancements, the characterization of the disease supporting cytokine network in PV has yet to be fully elucidated. It is overwhelmingly suggested that PV is a TH2-mediated disease, confirmed by the majority of studies demonstrating an increase in TH2-type cytokines. Recently, a focus has been placed on the contribution of the newly discovered TH17 subset to autoimmune states, and current evidence suggests that this inflammatory pathway may play a role in PV as well. Anti-cytokine medications are on the forefront as potential therapeutic options, and the growing number of reports of clinical benefit serves to confirm the major contribution of various inflammatory mediators in the development of disease phenotype. This work aimed to comprehend the complexity of cytokine and T cell involvement in pemphigus, taking account of known information and emphasizing the areas where additional research would be of great benefit, particularly in pharmacological development and expansion of the pemphigus therapeutic armamentarium.

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Section: Thmentioning

confidence: 88%

Cytokine networks in Pemphigus vulgaris: An integrated viewpoint

Giordano

Sinha

2012

Autoimmunity

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“…The normal blood circulating level of IL-6 is nearly 1 pg/ml [45,46], but an increase in its level is found under several conditions such as acute hyperglycemia [47], high-fat meal [48], normal menstrual cycle [49], physical activity [50] and during/after surgery [51]. Inconsistent levels of IL-6 have also been observed during pregnancy, with median values around 128 pg/ml registered at delivery, which drop by more than two fold (∼58 pg/ml) immediately afterward [52].…”

Section: Il6 Expression and Secretionmentioning

confidence: 99%

Role of interleukin-6 in cancer progression and therapeutic resistance

et al. 2016

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In the last several decades, the number of people dying from cancer-related deaths has not reduced significantly despite phenomenal advances in the technologies related to diagnosis and therapeutic modalities. The principal cause behind limitations in the curability of this disease is the reducing sensitivity of the cancer cells towards conventional anticancer therapeutic modalities, particularly in advance stages of the disease. Amongst several reasons, certain secretory factors released by the tumour cells into the microenvironment have been found to confer resistance towards chemo- and radiotherapy, besides promoting growth. Interleukin-6 (IL-6), one of the major cytokines in the tumour microenvironment, is an important factor which is found at high concentrations and known to be deregulated in cancer. Its overexpression has been reported in almost all types of tumours. The strong association between inflammation and cancer is reflected by the high IL-6 levels in the tumour microenvironment, where it promotes tumorigenesis by regulating all hallmarks of cancer and multiple signalling pathways, including apoptosis, survival, proliferation, angiogenesis, invasiveness and metastasis, and, most importantly, the metabolism. Moreover, IL-6 protects the cancer cells from therapy-induced DNA damage, oxidative stress and apoptosis by facilitating the repair and induction of countersignalling (antioxidant and anti-apoptotic/pro-survival) pathways. Therefore, blocking IL-6 or inhibiting its associated signalling independently or in combination with conventional anticancer therapies could be a potential therapeutic strategy for the treatment of cancers with IL-6-dominated signalling.

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“…On the other hand, rs2304365, as well as two other SNPs found to be significantly associated with PV in the original GWAS (rs4074067 and rs10504140; Table 1), map to the ST18 gene. ST18 encodes a transcription factor that regulates inflammation and apoptosis (Yang et al, 2008), two processes of direct relevance to the pathogenesis of PV (Ameglio et al, 1999;Bhol et al, 2001;Narbutt et al, 2008;Javor et al, 2009;Schmidt and Waschke, 2009;Bektas et al, 2010). As noted in Table 1, allele frequency of rs2304365 reached statistical significance in the replication set in a homozygous state only (odds ratio ¼ 6.55, one-sided P ¼ 0.02), supporting a recessive inheritance model for the disease risk causative sequence variant.…”

Section: Replication Studiesmentioning

confidence: 99%

Population-Specific Association between a Polymorphic Variant in ST18, Encoding a Pro-Apoptotic Molecule, and Pemphigus Vulgaris

Sarig

Bercovici

Zoller

et al. 2012

Journal of Investigative Dermatology

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Pemphigus vulgaris (PV) is a severe autoimmune blistering disease caused by anti-epithelial antibodies, leading to disruption of cell-cell adhesion. Although the disease is exceedingly rare worldwide, it is known to be relatively prevalent in Jewish populations. The low prevalence of the disease represents a significant obstacle to a genome-wide approach to the mapping of susceptibility genes. We reasoned that the study of a genetically homogeneous cohort characterized by a high prevalence of PV may help exposing associated signals while reducing spurious results due to population sub-structure. We performed a genome-wide association study using 300K single-nucleotide polymorphisms (SNPs) in a case-control study of 100 PV patients of Jewish descent and 397 matched control individuals, followed by replication of significantly associated SNPs in three additional cohorts of Jewish, Egyptian, and German origin. In addition to the major histocompatibility complex locus, a genomic segment on 8q11.23 that spans the ST18 gene was also found to be significantly associated with PV. This association was confirmed in the Jewish and Egyptian replication sets but not in the German sample, suggesting that ST18-associated variants may predispose to PV in a population-specific manner. ST18 regulates apoptosis and inflammation, two processes of direct relevance to the pathogenesis of PV. Further supporting the relevance of ST18 to PV, we found this gene to be overexpressed in the skin of PV patients as compared with healthy individuals.

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Serum Concentration of Interleukin-6 Is Increased Both in Active and Remission Stages of Pemphigus Vulgaris

Cited by 34 publications

References 21 publications

Cytokine networks in Pemphigus vulgaris: An integrated viewpoint

Cytokine networks in Pemphigus vulgaris: An integrated viewpoint

Role of interleukin-6 in cancer progression and therapeutic resistance

Population-Specific Association between a Polymorphic Variant in ST18, Encoding a Pro-Apoptotic Molecule, and Pemphigus Vulgaris

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