Specific interleukin-1 gene polymorphisms in Turkish patients with Behçet's disease

Abstract: Genetic factors that predispose individuals to Behçet's disease (BD) are considered to play important roles in the development of the disease. The pro‐inflammatory cytokine interleukin‐1 (IL‐1) has been implicated in the pathogenesis of BD. Our aim was to determine a possible association of specific polymorphisms of IL‐1α, IL‐1β, and IL‐1 receptor antagonist genes with susceptibility for BD. We genotyped 72 patients with BD and 163 healthy controls for IL‐1α?889, IL‐1β?511, and +3953 (nt5887) single‐nucleotide polymorphisms besides IL‐1 receptor antagonist variable number of tandem repeat polymorphism (for five different alleles). Comparison of the IL‐1β+3953 T allele and TT genotype frequencies showed a significant difference between patients with BD and controls (54.2 vs. 40.5%, OR = 1.74, P = 0.024, and 40.3 vs. 19.6%, OR = 2.76, P = 0.009, respectively). However, no difference was observed in the genotype or allele frequencies of IL‐1α?889, IL‐1β?511, and IL‐1 receptor antagonist between the patients with BD and the controls. Our results indicate that susceptibility to BD is increased in individuals carrying the IL‐1β+3953 T allele and TT genotype.     

Elevated levels of tumour necrosis factor (TNF)-α, interleukin (IL)-1β and IL-10 in hidradenitis suppurativa skin: a rationale for targeting TNF-α and IL-1β

Background The pathogenesis of hidradenitis suppurativa (HS) is largely unknown and the disease is difficult to treat. Patients are in high need of an effective treatment. Although it is not known whether the levels of tumour necrosis factor (TNF)‐α are aberrant in HS skin, anti‐TNF‐α biologics are used, with variable clinical efficacy. Objectives To determine the cytokine profile in lesional and perilesional HS skin. Methods We cultured 20 lesional and 10 normal‐appearing perilesional HS skin samples, seven psoriasis and six healthy control skin samples in a transwell culture system. Two distinct cytokine bead arrays were used to measure the spectrum of inflammatory cytokines in the culture supernatant. Results from HS skin samples were compared with those of healthy and psoriasis skin. Results The proinflammatory cytokines interleukin (IL)‐1β and TNF‐α as well as the anti‐inflammatory cytokine IL‐10 were significantly elevated in HS skin. Elevated levels of these cytokines were also found in perilesional HS skin. Fold increases relative to control skin of IL‐1β, TNF‐α and IL‐10 in HS were 31, 5 and 34, compared with psoriasis: 4, 1 and 2, respectively. Levels of all three cytokines showed a trend towards a positive correlation with disease severity. IL‐2, IL‐4, IL‐5 and interferon‐γ were hardly detectable in HS or healthy control skin. Conclusions This study shows for the first time that IL‐1β, TNF‐α and IL‐10 levels are elevated in HS skin. These data provide a rationale for therapies with biologics targeting cytokines such as TNF‐α and IL‐1.     

Genetic predisposition to parthenium dermatitis in an Indian cohort due to lower-producing genotypes of interleukin-10 (-) 1082 G>A and (-) 819 C>T loci but no association with interferon-γ (+) 874 A>T locus

Summary Background Parthenium dermatitis is an activated T cell‐mediated type IV hypersensitivity. Its pathogenesis is well characterized, with interindividually varying serum levels of pro‐ and anti‐inflammatory and regulatory T‐cell cytokines and coherently perturbed cross‐regulation between them. The functional single nucleotide polymorphisms (SNPs) in these cytokine genes might function as risk/susceptibility factors for the disease. Objectives We analysed the serum levels of interferon (IFN)‐γ and interleukin (IL)‐10 cytokines in cases vs. controls and investigated whether IFN‐γ (+) 874 A>T and IL‐10 (?) 1082 G>A and (?) 819 C>T are associated with serum levels and genetically predispose to the disease. Methods The study included 60 patch test‐confirmed patients and 60 age‐ and sex‐matched controls. The serum levels of cytokines were estimated by high‐sensitivity enzyme‐linked immunosorbent assay kits. SNP genotyping was performed by amplification refractory mutational system–polymerase chain reaction. Results In patients, the serum level of IFN‐γ was significantly increased and that of IL‐10 was significantly decreased, with no difference in IgE concentration. Genetically no IFN‐γ (+) 874 A>T alleles/genotypes were associated with the disease, but a strong predisposition was found due to lower‐producing genotypes of IL‐10 (?) 1082 G>A and (?) 819 C>T SNPs, with 2·1 and 3·5 times more risk, respectively, while intermediate IL‐10‐producing genotypes provided resistance. Conclusions High serum IFN‐γ might play a role in disease pathogenesis, but this is genetically not endowed by the IFN‐γ SNP studied. In contrast, low serum IL‐10 was very much connected, with the genetics of both studied IL‐10 loci. These might be key managing factors concerning pathogenesis/susceptibility.     

Immunoregulatory effects of isotretinoin in patients with acne

Background In vitro studies have shown that retinoids influence T‐cell differentiation. Objectives To study the effect of isotretinoin on T‐cell differentiation markers in patients with acne. Methods A total of 37 patients with acne vulgaris (25 female, 12 male, age 19·6 ± 3·7 years) and 30 age‐ and sex‐matched healthy controls (19 female, 11 male, age 20·5 ± 4·4 years) were included in the study. Screening for biochemical parameters in serum samples were done just before initiation (pretreatment) and after 3 months of isotretinoin treatment (post‐treatment) in the acne group. Results Baseline levels of tumour necrosis factor (TNF)‐α (P < 0·0001), interleukin (IL)‐4 (P < 0·0001), IL‐17 (P < 0·0001) and interferon (IFN)‐γ (P = 0·002) were significantly higher in the acne group compared with the control group. TNF‐α (P < 0·0001), IL‐4 (P < 0·0001), IL‐17 (P < 0·0001) and IFN‐γ (P < 0·0001) levels decreased after isotretinoin treatment. TNF‐α and IL‐4 values after isotretinoin treatment were similar to those of the control group. However, levels of IL‐17 (P < 0·0001) after isotretinoin treatment were higher than those of the control group, despite a significant decline after treatment. Levels of IFN‐γ (P < 0·0001) after isotretinoin treatment were lower than those of the control group. Conclusions This study shows that isotretinoin treatment significantly decreases TNF, IL‐4, IL‐17 and IFN‐γ levels in patients with acne. We failed to show that isotretinoin redirects naive T helper (Th) differentiation preferentially towards the Th2 cell lineage.     

Interferon‐γ induces upregulation and activation of the interleukin‐31 receptor in human dermal microvascular endothelial cells

Abstract: Interleukin‐31 (IL‐31), a recently discovered cytokine derived from T helper cells, is involved in chronic dermatitis and pruritus. This study demonstrates for the first time that the IL‐31 receptor complex for IL‐31 is substantially upregulated in human dermal microvascular endothelial cells after stimulation with interferon‐γ (IFN‐γ). Activation of the IL‐31 receptor complex results in the induction of the intracellular ERK1/2 signaling pathway and downregulation of IFN‐γ‐induced monokine induced by IFN‐γ expression. Inhibitor studies revealed that the IFN‐γ‐induced IL‐31RA upregulation is processed via JNK and PI3 kinase activation. In sum, our study points toward an interaction between the T_H1‐derived cytokine IFN‐γ and the T_H2‐derived cytokine IL‐31 on endothelial cells.     

Adalimumab (antitumour necrosis factor-α) treatment of hidradenitis suppurativa ameliorates skin inflammation: an in situ and ex vivo study

Background Hidradenitis suppurativa (HS) is a difficult‐to‐manage disease. Randomized controlled trials with antitumour necrosis factor (TNF)‐α biologics have been conducted and in most studies disease activity was reduced. However, the mechanism of action in HS skin is so far unknown. Objectives To assess whether anti‐TNF‐α treatment affects in situ cytokine production and frequency of inflammatory cell populations in HS lesional skin. Methods Nine patients with HS, participating in a larger placebo‐controlled, double‐blind phase IIb clinical trial on the efficacy and safety of adalimumab in patients with moderate to severe HS (M10‐467), were randomized and treated for 16 weeks. In a mechanism‐of‐action substudy, biopsies were obtained at fixed time points pre‐ and post‐treatment. One part of the biopsy was cultured for 24 h for cytokine release in the culture medium, while another part was used for in situ analysis. Results Secretion of cytokines, including interleukin (IL)‐1β, CXCL9 [monokine induced by interferon‐γ (MIG)], IL‐10, IL‐11, B‐lymphocyte chemoattractant (BLC) and IL‐17A, was significantly elevated in HS. Adalimumab treatment was associated with decreased production of cytokines in HS skin, especially IL‐1β, CXCL9 (MIG) and BLC. Treatment significantly reduced the number of CD11c+, CD14+ and CD68+ cells in HS lesional skin. The numbers of CD3+ and CD4+ T cells, and CD20+ and CD138+ B cells were also reduced by adalimumab treatment. Conclusions Adalimumab treatment inhibits important cytokines and inflammatory cell numbers in lesional HS skin, especially levels of IL‐1β and numbers of inflammatory CD11c+ dendritic cells.     

TNF‐α and IL‐10 gene polymorphisms show a weak association with pemphigus vulgaris in the Slovak population

Backround Pemphigus vulgaris is a rare chronic autoimmune disease of skin and mucous membranes, with several cytokines participating in its development. The role of their gene polymorphisms in susceptibility to the disease is, however, not fully understood. Objective The aim of our case‐control study was to investigate whether some of 22 single nucleotide polymorphisms (SNPs) in 13 cytokine genes (IL‐1α, IL‐1β, IL‐1RI, IL‐1Ra, IL‐4Rα, IL‐12, IFN‐γ, TGF‐β1, TNF‐α, IL‐2, IL‐4, IL‐6 and IL‐10) are associated with pemphigus vulgaris in the Slovak population. Methods DNA samples were obtained from 34 pemphigus vulgaris patients and 140 healthy controls of Slovak origin. Cytokine gene SNPs were determined using the polymerase chain reaction with sequence‐specific primers (PCR‐SSP) method. Results We found a weak association between pemphigus vulgaris and polymorphic variants in TNF‐α and IL‐10 genes only, with haplotypes TNF‐α–308G/–238G and IL‐10 –1082A/–819C/–592C being significantly overrepresented in pemphigus vulgaris patients (TNF‐α GG: 94.12% vs. 82.86%, P = 0.0216; IL‐10 ACC: 44.12% vs. 30.00%, P = 0.0309). Conclusions Our preliminary results suggest that certain TNF‐α and IL‐10 gene polymorphisms might contribute to genetic susceptibility to pemphigus vulgaris; however, their overall impact on disease development will be rather limited.     

Cytokine gene polymorphisms in atopic dermatitis

BACKGROUND: Atopic dermatitis (AD) and psoriasis are genetically determined inflammatory skin disorders characterized by abnormal cytokine production. From association studies there is evidence that functionally relevant cytokine gene polymorphisms contribute to the genetic basis of psoriasis. Association studies in AD have mostly been limited to polymorphisms of T-helper 2-type cytokines, which dominate in acute AD lesions. Unexpectedly, the results of recent genome scans indicate linkage of AD to psoriasis susceptibility loci. Therefore, AD may also be influenced by genes that modulate cutaneous inflammation independently from atopic mechanisms. OBJECTIVES: To investigate further the role of cytokine gene polymorphisms in AD. METHODS: Polymorphisms in the genes encoding tumour necrosis factor-alpha (TNFA-238 G/A, -308 G/A), interleukin (IL)-1beta (IL1B-511 T/C, +3953 T/C), IL-6 (IL6-174 C/G), IL-10 (IL10-1082 A/G) and the IL-1 receptor antagonist (IL1RN intron 2) were investigated in German patients with AD (n = 94) and in healthy nonatopic individuals (n = 214) by polymerase chain reaction-based methods and direct cycle sequencing. RESULTS: No association was found between AD and any of the polymorphisms analysed. This is in contrast to the recently described association between psoriasis and the TNFA-238 and IL1B-511 polymorphisms. CONCLUSIONS: Our data indicate that cytokine gene polymorphisms may act as specific markers of inflammatory skin diseases rather than contribute to a general disposition towards cutaneous inflammation.     

Open-label study of the efficacy and safety of topical treatment with TDT 067 (terbinafine in Transfersome®) in patients with onychomycosis

Background Alopecia areata (AA) is the second most common cause of hair loss in humans, and has a genetically complex inheritance. The hypothesis that AA is autoimmune in nature is supported by previous studies. These report an association with specific HLA alleles, as well as genetic variants of other genes implicated in autoimmunity, such as various cytokine genes. However, these cannot yet be considered proven susceptibility loci, as many of these association findings were derived from small patient samples. Objectives To investigate the association between AA and selected cytokine genes using a sample of 768 patients with AA and 658 controls of Central European origin. Methods Eleven single‐nucleotide polymorphisms (SNPs) from cytokine genes implicated in previous AA studies were genotyped. These genes were IL1B, IL1A, IL1RN, MIF, IFNG and the TNF/LTA gene region. We also genotyped 15 SNPs selected from cytokine genes that have shown significant association with other autoimmune diseases. These genes were IL10, IL36RN, IL12B, IL6, IL2, IL23, IL2RA and IL4R. Results Significant association was found for two variants within both IL2RA and TNF/LTA. In the overall sample, the most significant results were obtained for the IL2RA variant rs706778 (P = 0·00038) and the TNF/LTA locus variant rs1800629 (P = 0·0017). In subgroup analyses, according to severity, age at onset and family history these effects were stronger in the severely affected patients, with the lowest P‐values being obtained for rs706778 (P = 3·8 × 10^?6). Conclusions Our results point to the involvement of IL2RA and the TNF/LTA region in the aetiology of AA, in particular severe AA, and provide further support for the hypothesis that AA is autoimmune in nature.     

Elevation of serum epidermal growth factor and interleukin 1 receptor antagonist in active psoriasis vulgaris

Background Psoriatic plaques present a complex expression profile, including high levels of cytokines, chemokines and growth factors. Circulating cytokines have been suggested to reflect the activation status of the inflammatory process. Objectives To analyse 20 cytokines, chemokines and growth factors in 14 patients with psoriasis vulgaris at the start and during the course of ultraviolet B treatment. Methods A multiplex cytokine assay was used. Results We identified increased serum levels of epidermal growth factor (EGF) (mean 323 vs. 36·6 pg mL^?1, P =0·0001), interleukin (IL)‐1 receptor antagonist (mean 39·1 vs. 14·6 pg mL^?1, P =0·02) and tumour necrosis factor‐α (mean 7·5 vs. 4·5 pg mL^?1, P =0·04) at baseline in patients with psoriasis compared with matched controls. None of these cytokines was correlated to the severity of the disease (Psoriasis Area and Severity Index) or decreased with phototherapy, suggesting that sources other than lesional skin contribute to the production of these cytokines. Using cluster analysis, we observed coordinate upregulation of EGF, IL‐6, macrophage inflammatory protein‐1β and vascular endothelial growth factor. Conclusions The sustained high expression of inflammatory circulating cytokines is a potential mechanism linking psoriasis with its extracutaneous comorbidities.     

Cytokine profile during the clinical course of toxic shock syndrome

Toxic shock syndrome (TSS) is an acute febrile disease with multiple organ involvement caused by massive and rapid release of cytokines induced by staphylococcal exotoxins. However, the precise cytokine profile is still undefined in clinical cases. We measured serum cytokine concentrations in a patient who developed TSS after a caesarean section. Measurements were taken on admission and several times during the course of the disease. Methicillin‐resistant Staphylococcus aureus producing TSS toxin‐1 and staphylococcal enterotoxin C was detected in the lochia and venous blood. Serum interleukin (IL)‐6 level was markedly increased on admission, and IL‐10, tumour necrosis factor‐α, and interferon‐γ levels were also raised. These cytokine levels rapidly returned to normal levels. In contrast, IL‐1β and IL‐2 were below the analytical sensitivity threshold throughout the course. Our data and other previous case reports indicate that a marked increase in IL‐6 concentration could be a clinical marker of TSS onset.     

Markers of systemic inflammation in psoriasis: a systematic review and meta‐analysis

Studies investigating systemic inflammation in psoriasis use different serum markers and report discrepant results. We set out to determine whether systemic inflammation is elevated in patients with psoriasis compared with healthy controls, and to measure the extent of this elevation, by summarizing available data on serum inflammatory markers. PubMed, Embase and Web of Science were searched from inception to March 2011. We included studies comparing the serum inflammatory markers interleukin (IL)‐1β, IL‐6, IL‐10, C‐reactive protein (CRP), intracellular adhesion molecule (ICAM)‐1, E‐selectin and tumour necrosis factor (TNF)‐α in patients with psoriasis and healthy controls. Differences in serum marker levels between patients and controls were pooled as standardized mean differences (SMDs; Cohen's d) using a random‐effects model. Seventy‐eight studies were eligible. Of the 7852 individuals included, 3085 had (severe plaque) psoriasis. The pooled SMDs were higher in patients with psoriasis than in healthy controls for IL‐6 [d = 1·32, 95% confidence interval (CI) 0·83–1·81], CRP (d = 1·83, 95% CI 0·76–2·90), TNF‐α (d = 1·32, 95% CI 0·86–1·79), E‐selectin (d = 1·78, 95% CI 1·32–2·25) and ICAM‐1 (d = 1·77, 95% CI 1·15–2·39). The SMD between cases and controls for IL‐1β and IL‐10 was not significant. Age had a significant effect on the SMD for IL‐6 and TNF‐α. For IL‐6 the effect size was higher for plaque psoriasis studies (d = 1·98). The effect size was not influenced by the Psoriasis Area and Severity Index, measurement method or quality assessment. The pooled analyses suggest modest but significantly elevated levels of the proinflammatory cytokines in the serum of patients with psoriasis with predominantly severe disease. To what extent this modest increment is clinically relevant could be investigated in a synthesis of all studies measuring inflammation before and after antipsoriatic therapy.     

In vitro diagnostic assays are effective during the acute phase of delayed‐type drug hypersensitivity reactions

Background Previous reports have suggested that drug‐specific lymphocyte proliferation assays (LPA) can be used retrospectively to confirm the culprit drug following delayed‐type drug hypersensitivity reactions (DHR). However, only limited evidence supports their use in aiding acute clinical management. The aim of this study was to compare the LPA against combination cytokine assays for potential use in the acute setting. Methods A total of 43 patients with DHR (19 during the acute reaction, 20 after recovery, four during acute and after recovery) and 14 control subjects without DHR were investigated using ex vivo analysis of drug‐specific proliferation, and interferon (IFN)‐γ and interleukin (IL)‐4 production. Results Healthy controls showed negative drug‐specific proliferation and cytokine release in contrast to individuals with a known sensitivity (P < 0·0001). The assays demonstrated a test specificity of 95% (LPA), 83% (IFN‐γ) and 92% (IL‐4). The sensitivity of combined measurement of drug‐specific IFN‐γ and IL‐4 cytokines during acute DHR was better than LPA (82% vs. 50%), but all assays were less sensitive during the recovery phase. The correlation between LPA and IFN‐γ assays was strong (r = 0·7, P < 0·0001), whereas the IL‐4 assay did not correlate as well with either of these assays. In contrast to LPA, drug enzyme‐linked immunosorbent spot assays showed positive responses in patients concurrently taking immunosuppressive medication. Conclusions In vitro assays of drug‐specific IFN‐γ and IL‐4 production offer potential for use as rapid diagnostic tests. Cytokine detection offers distinct advantages over the LPA, including a shorter assay time, a greater sensitivity and effectiveness in testing immunosuppressed patients.     

Nicotinamide downregulates gene expression of interleukin‐6, interleukin‐10, monocyte chemoattractant protein‐1, and tumour necrosis factor‐α gene expression in HaCaT keratinocytes after ultraviolet B irradiation

Ultraviolet (UV) radiation has profound effects on human skin, causing sunburn, inflammation, cellular‐tissue injury, cell death, and skin cancer. Most of these effects are mediated by a number of cytokines produced by keratinocytes. In this study we investigated whether nicotinamide (NCT), the amide form of vitamin B3, might have a protective function in reducing the expression of interleukin (IL)‐1β, IL‐6, IL‐8, IL‐10, monocyte chemoattractant protein (MCP)‐1 and tumour necrosis factor (TNF)‐α in UV‐irradiated keratinocytes. HaCaT cells were treated with UVB in the presence or absence of NCT, and cytokine mRNA levels were examined by quantitative real‐time PCR. NCT significantly downregulated IL‐6, IL‐10, MCP‐1 and TNF‐α mRNA expression, whereas it did not exert any significant effect on IL‐1β or IL‐8 expression. Because of its ability to decrease these cytokine mediators after UV exposure, NCT is a possible therapy to improve or prevent conditions induced or aggravated by UV light.     

Evidence for a regulatory loop between IFN‐γ and IL‐33 in skin inflammation

Interleukin‐33 has recently gained much attention due to its role in allergic responses. It has been shown to amplify Th2 responses and to act as a damage‐associated molecular pattern. IL‐33 acts on a broad range of cells and has been proposed to link innate and adaptive features of allergic responses. It was the aim of this study to investigate this property of IL‐33 in the inflammatory response characterising atopic dermatitis (AD). We have analysed the response of skin‐resident cells derived from patients with AD and healthy donors with regard to the expression of IL‐33 and its receptor ST2. The functional impact of IL‐33 on CD4+ T cells was investigated. Keratinocytes and dermal fibroblasts clearly differ in their regulation of IL‐33. In fibroblasts, the concerted action of TNF‐α and IL‐1β was the strongest inducer, whereas IFN‐γ is clearly the key molecule that upregulates IL‐33 in keratinocytes with a more pronounced response of cells derived from patients with AD. Keratinocytes from patients with AD showed a markedly higher constitutive expression level of surface ST2. CD4+ T cells respond to IL‐33. Unexpectedly, IL‐33 failed to induce a significant secretion of IL‐5 or IL‐13. By contrast, high amounts of IFN‐γ were detectable if IL‐33 was added to the T‐cell receptor‐stimulated cells or in combination with IL‐12. These results suggest that IL‐33 and IFN‐γ are closely interlinked in epidermal AD inflammation. IFN‐γ induces IL‐33 in keratinocytes and IL‐33 acts on activated T cells to further increase the release of IFN‐γ, therefore contributing to drive skin inflammation towards chronic responses.     

Psoriasis and melanocytic naevi: does the first confer a protective role against melanocyte progression to naevi?

Background Some of the cytokines that have effects on melanogenesis are also reported to be involved in psoriasis. Objectives We therefore studied the relationship between psoriasis and melanocytic naevi. In particular, the aim of our study was to investigate the number of melanocytic naevi in patients with psoriasis vs. controls. Methods We performed a prospective case–control study, analysing 93 adult patients with psoriasis and 174 adult aged‐matched controls. For each participant a questionnaire was completed to establish personal data, personal medical history, and personal and familial history of skin cancer and psoriasis. We analysed interleukin (IL)‐1α, IL‐6 and tumour necrosis factor (TNF)‐α gene expression at the peripheral blood mononuclear cell level in patients with psoriasis and in controls. Results In our study, patients with psoriasis presented a lower number of areas with naevi in comparison with controls (P < 0·0001). Nobody had ever had squamous cell carcinoma or melanoma in the psoriatic group; moreover, there was a significant difference in familial history of melanoma between the two groups (none in the psoriatic group vs. 8% in the control group; P < 0·05). IL‐1α, IL‐6 and TNF‐α expression levels were higher in patients with psoriasis. Conclusions People with psoriasis had fewer melanocytic naevi. This suggests that the proinflammatory cytokine network in psoriasis skin might inhibit melanogenesis, melanocyte growth and/or progression to naevi.     

UVA‐1 exposure in vivo leads to an IL‐6 surge within the skin

UVA‐1 is a known promotor of skin ageing. Cytokines like IL‐1α, Il‐1β or TNF‐α, VEGF and IL‐6 orchestrate UV effects, and IL‐6 is furthermore an effector of UVA‐induced photoageing. We investigated how fractionated UVA‐1 doses influence the cytokine milieu and especially the IL‐6 levels in the skin in vivo. In a study with 35 participants, we exposed previously unirradiated human skin to three UVA‐1 irradiation regimes. Cytokine levels in interstitial skin fluid were measured up to 48 hours postexposure and compared to unirradiated control skin fluid. Our results show that IL‐6 levels increased significantly after UVA‐1 exposure at selected time points. The other candidates IL‐1α, Il‐1β or TNF‐α and VEGF show no significant response after UVA‐1 exposure in vivo. UVA‐1 thus raises selectively IL‐6 levels in vivo, a fact that underlines its role in photoageing and has potential implications for its modulatory effect on photoageing pathology.     

Assessment of transcriptional activity genes associated with the IL‐17 signaling pathway in skin fibroblasts under the influence of adalimumab

It is believed that IL‐17 is involved in the signaling pathways of nuclear factor κB (NFκB) and mitogen‐activated kinases (MAPKs). Adalimumab, a full anti‐TNF‐α monoclonal antibody, was used for treatment of moderate to severe psoriasis. This study aimed to investigate the effect of adalimumab on changes in the expression of genes associated with IL‐17 signaling pathways in normal human dermal fibroblast (NHDF) culture. NHDFs treated with adalimumab at 2, 8, and 24 hr were compared with those of control. Microarray technique and PANTHER program were used to determine the expression of genes. The number of mRNA IDs differentiating the culture displayed on adalimumab in comparison with the control culture (?3.0 < FC > + 3.0) was as follows: H‐2—32 mRNA ID, H‐8—3 mRNA ID, H‐2 and H‐8—47 mRNA ID, H‐8 and H‐24—1 mRNA ID. Analysis by the PANTHER program indicated that adalimumab significantly affects the six signaling pathways and 19 biological processes associated with IL‐17. The strongest changes in the expression profile concerned pathway genes associated with the chemokine and cytokine signaling pathway, the gonadotropin‐releasing hormone receptor pathway, and the CCKR signaling map.