Uluckan et al. IL-17A causes local skin inflammation and accelerates bone loss

IBMS BoneKEy ◽  
2016 ◽  
Vol 13 ◽  
pp. 835
Keyword(s):  
Bone Loss ◽  
Skin Inflammation ◽  
Local Skin

scholarly journals Local Skin Inflammation in Cutaneous Leishmaniasis as a Source of Variable Pharmacokinetics and Therapeutic Efficacy of Liposomal Amphotericin B

2018 ◽  
Vol 62 (10) ◽  
Author(s):  
Gert-Jan Wijnant ◽  
Katrien Van Bocxlaer ◽  
Amanda Fortes Francisco ◽  
Vanessa Yardley ◽  
Andy Harris ◽  
...  
Keyword(s):  
Cutaneous Leishmaniasis ◽  
Amphotericin B ◽  
Liposomal Amphotericin ◽  
Skin Inflammation ◽  
Skin Lesions ◽  
Disease Stage ◽  
Liposomal Amphotericin B ◽  
Local Skin ◽  
Content Type ◽  
Tissue Inflammation

ABSTRACTDisfiguring skin lesions caused by several species of theLeishmaniaparasite characterize cutaneous leishmaniasis (CL). Successful treatment of CL with intravenous (i.v.) liposomal amphotericin B (LAmB) relies on the presence of adequate antibiotic concentrations at the dermal site of infection within the inflamed skin. Here, we have investigated the impact of the local skin inflammation on the pharmacokinetics (PK) and efficacy of LAmB in two murine models of localized CL (Leishmania majorandLeishmania mexicana) at three different stages of disease (papule, initial nodule, and established nodule). Twenty-four hours after the administration of one 25 mg/kg of body weight LAmB (i.v.) dose to infected BALB/c mice (n= 5), drug accumulation in the skin was found to be dependent on the causative parasite species (L. major>L. mexicana) and the disease stage (papule > initial nodule > established nodule > healthy skin). Elevated tissue drug levels were associated with increased vascular permeability (Evans blue assay) and macrophage infiltration (histomorphometry) in the infected skin, two pathophysiological parameters linked to tissue inflammation. After identical treatment of CL in the two models with 5 × 25 mg/kg LAmB (i.v.), intralesional drug concentrations and reductions in lesion size and parasite load (quantitative PCR [qPCR]) were all ≥2-fold higher forL. majorthan forL. mexicana. In conclusion, drug penetration of LAmB into CL skin lesions could depend on the disease stage and the causativeLeishmaniaspecies due to the influence of local tissue inflammation.

scholarly journals Inflammatory Arthritis, Sacroiliitis, and Morphea: Evidence of a Systemic Inflammatory Disease

2013 ◽  
Vol 2013 ◽  
pp. 1-3
Author(s):  
Mohammed A. Omair ◽  
Sindhu R. Johnson
Keyword(s):  
Inflammatory Disease ◽  
Skin Disease ◽  
Inflammatory Arthritis ◽  
Skin Inflammation ◽  
Skin Lesions ◽  
Local Skin ◽  
Systemic Inflammatory Disease ◽  
Inflammatory Polyarthritis ◽  
New Skin

Morphea is a skin disease characterized by local skin inflammation and fibrosis. Extracutaneous manifestations have been described with this disease including inflammatory arthritis. We describe a case of morphea who developed inflammatory polyarthritis and sacroiliitis coincident with new skin lesions.

scholarly journals Huangbai Liniment Ameliorates Skin Inflammation in Atopic Dermatitis

2021 ◽  
Vol 12 ◽  
Author(s):  
Ting Zheng ◽  
Miao Fan ◽  
Yunbo Wei ◽  
Jinhong Feng ◽  
Pengcheng Zhou ◽  
...  
Keyword(s):  
Immune Response ◽  
Atopic Dermatitis ◽  
Mouse Model ◽  
Skin Diseases ◽  
Skin Inflammation ◽  
Local Skin ◽  
Immune Balance ◽  
Type 2 Immune Response ◽  
Ad Mouse Model

Atopic dermatitis (AD), also known as atopic eczema, is one of the most common skin diseases and is characterized by allergic skin inflammation, redness, and itchiness and is associated with a hyperactivated type 2 immune response. The leading causes of AD include an imbalance in the immune system, genetic predisposition, or environmental factors, making the development of effective pharmacotherapies complex. Steroids are widely used to treat AD; however, they provide limited efficacy in the long term and can lead to adverse effects. Thus, novel treatments that offer durable efficacy and fewer side effects are urgently needed. Here, we investigated the therapeutic potential of Huangbai Liniment (HB), a traditional Chinese medicine, using an experimental AD mouse model, following our clinical observations of AD patients. In both AD patient and the mouse disease model, HB significantly improved the disease condition. Specifically, patients who received HB treatment on local skin lesions (3–4 times/day) showed improved resolution of inflammation. Using the 1-Chloro-2,4-dinitrobenzene (DNCB)-induced AD model in BALB/c mice, we observed that HB profoundly alleviated severe skin inflammation and relieved the itching. The dermatopathological results showed markedly reversed skin inflammation with decreased epidermal thickness and overall cellularity. Correspondingly, HB treatment largely decreased the mRNA expression of proinflammatory cytokines, including IL-1β, TNF-α, IL-17, IL-4, and IL-13, associated with declined gene expression of IL-33, ST2, and GATA3, which are connected to the type 2 immune response. In addition, HB restored immune tolerance by promoting regulatory T (TREG) cells and inhibiting the generation of TH1, TH2, and TH17 cells in vitro and in the DNCB-induced AD mouse model. For the first time, we demonstrate that HB markedly mitigates skin inflammation in AD patients and the DNCB-induced AD mouse model by reinvigorating the T cell immune balance, shedding light on the future development and application of novel HB-based therapeutics for AD.

Chronic skin inflammation leads to bone loss by IL-17–mediated inhibition of Wnt signaling in osteoblasts

2016 ◽  
Vol 8 (330) ◽  
pp. 330ra37-330ra37 ◽  
Author(s):  
Özge Uluçkan ◽  
Maria Jimenez ◽  
Susanne Karbach ◽  
Anke Jeschke ◽  
Osvaldo Graña ◽  
...  
Keyword(s):  
Bone Loss ◽  
Wnt Signaling ◽  
Skin Inflammation ◽  
Chronic Skin

scholarly journals Apremilast Microemulsion as Topical Therapy for Local Inflammation: Design, Characterization and Efficacy Evaluation

2020 ◽  
Vol 13 (12) ◽  
pp. 484
Author(s):  
Paulo Sarango-Granda ◽  
Marcelle Silva-Abreu ◽  
Ana Calpena ◽  
Lyda Halbaut ◽  
María-José Fábrega ◽  
...  
Keyword(s):  
Topical Therapy ◽  
Skin Inflammation ◽  
In Vivo Model ◽  
Order Kinetic ◽  
Efficacy Evaluation ◽  
In Vivo Models ◽  
Local Skin ◽  
Anti Inflammatory

Apremilast (APR) is a selective phosphodiesterase 4 inhibitor administered orally in the treatment of moderate-to-severe plaque psoriasis and active psoriatic arthritis. The low solubility and permeability of this drug hinder its dermal administration. The purpose of this study was to design and characterize an apremilast-loaded microemulsion (APR-ME) as topical therapy for local skin inflammation. Its composition was determined using pseudo-ternary diagrams. Physical, chemical and biopharmaceutical characterization were performed. Stability of this formulation was studied for 90 days. Tolerability of APR-ME was evaluated in healthy volunteers while its anti-inflammatory potential was studied using in vitro and in vivo models. A homogeneous formulation with Newtonian behavior and droplets of nanometric size and spherical shape was obtained. APR-ME released the incorporated drug following a first-order kinetic and facilitated drug retention into the skin, ensuring a local effect. Anti-inflammatory potential was observed for its ability to decrease the production of IL-6 and IL-8 in the in vitro model. This effect was confirmed in the in vivo model histologically by reduction in infiltration of inflammatory cells and immunologically by decrease of inflammatory cytokines IL-8, IL-17A and TNFα. Consequently, these results suggest that this formulation could be used as an attractive topical treatment for skin inflammation.

scholarly journals Interleukin-8 Levels in the Stratum Corneum as a Biomarker for Monitoring Therapeutic Effect in Atopic Dermatitis Patients

2021 ◽  
pp. 1-15
Author(s):  
Susumu Murata ◽  
Sakae Kaneko ◽  
Eishin Morita
Keyword(s):  
Atopic Dermatitis ◽  
Topical Corticosteroid ◽  
Stratum Corneum ◽  
Corticosteroid Treatment ◽  
Skin Inflammation ◽  
Interleukin 8 ◽  
Tape Stripping ◽  
Therapeutic Effects ◽  
Local Skin ◽  
Before And After

<b><i>Introduction:</i></b> The stratum corneum contains several growth factors and cytokines that are synthesized in keratinocytes. We previously reported that the amount of interleukin-8 in the stratum corneum (scIL-8) is related to the severity of local skin inflammation in atopic dermatitis (AD). However, it is unknown whether scIL-8 levels reflect pharmacologic responses to a therapeutic intervention in AD patients. Therefore, in this study, we aimed to investigate whether the improvement of dermatitis in AD is correlated with scIL-8 levels before and after topical corticosteroid treatment. <b><i>Methods:</i></b> Stratum corneum samples were collected from 22 AD patients using the noninvasive tape-stripping method before treatment, 2 weeks after topical treatment, and 4–6 weeks after treatment. <b><i>Results:</i></b> scIL-8 levels on the forearm reduced significantly from 790 ± 348 pg/mg before treatment to 163 ± 68 pg/mg 2 weeks after treatment and 100 ± 37 pg/mg 4–6 weeks after corticosteroid treatment. scIL-8 levels on the abdomen also reduced significantly from 902 ± 391 to 142 ± 38 pg/mg at the end of study. The reduction in scIL-8 levels was associated with the improvement in local skin severity in AD. We also found that scIL-8 levels, along with blood biomarker levels (serum thymus and activation-regulated chemokine, lactate dehydrogenase, and %eosinophil), decreased significantly after the treatment. <b><i>Conclusion:</i></b> The scIL-8 concentration decreases with improvements in skin symptoms in AD patients after topical corticosteroid treatment; thus, it may be a suitable biomarker for monitoring therapeutic effects in AD patients.

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