interleukin-8 and Erythema

Rosacea changes are a result of an immune mediated response and the angiogenic properties of the LL-37 peptide. This peptide induces an inflammatory signal that activates the NLRP3-mediated inflammasome, triggering rosacea pathogenesis. Research findings show that LL-37 peptide is inhibited by binding to a cell surface glycosaminoglycan, heparan sulfate. Heparan Sulfate Analog (HSA) is a proprietary low molecular weight analog of heparan sulfate that has been formulated into a Dermal Repair Cream (DRC), specifically to aid in such immune mediated responses. Herein, in vitro studies using human epidermal keratinocytes showed an increase in HSA decreased LL-37 toxicity and IL-8 cytokine release. A single-center, randomized double-blind trial included 16 subjects (Fitzpatrick skin types I-IV) with a clinical diagnosis of type 1 rosacea and moderate to severe facial erythema, who were undergoing Pulsed Dye Laser (PDL) treatment. The clinical improvements of their facial erythema were assessed at baseline, 2 weeks, 4 weeks, and 8 weeks. Results revealed that low molecular weight HSA significantly improves the clinical signs of rosacea during the 8 weeks of use likely resulting from inhibition of LL-37 induced IL-8 cytokine release. These findings support the use of DRC in rosacea topical treatment regimens as it demonstrates visible skin benefits and improves tolerability of PDL therapy in a shorter duration of time as compared with PDL alone.George R, Gallo RL, Cohen JL, et al. Reduction of erythema in moderate-severe rosacea by a low molecular weight Heparan Sulfate Analog (HSA). J Drugs Dermatol. 2023;22(6):546-553. doi:10.36849/JDD.7494.

Topics: Cathelicidins; Erythema; Heparitin Sulfate; Humans; Interleukin-8; Molecular Weight; Rosacea; Treatment Outcome

Seborrheic dermatitis is a chronic inflammatory disease aggravated by Malassezia species. Toll-like receptors (TLR) are part of innate immune system that can be activated by yeasts. Previous studies showed that an association of Umbelliferae extract with a lipid (TLR2-Regul™) decreases the IL-8 expression in human skin in contact with M. furfur. The aim of this study was to assess the activity of a topical formulated with TLR2-Regul™ in the prevention of seborrheic dermatitis (SD) relapses.. Immune-competent SD adult patients were treated for SD (topical imidazoles or steroids). Cleared patients were randomized and received a topical containing TLR2-Regul™ (A) or its vehicle (B). Erythema, scales and pruritus were assessed during two months.. The study included 115 patients, mean age 43.4, sex ratio m/f 1.5. At week 4 the relapse rate was 26% (N.=15) in group A and 43% (N.=25) in group B. At W8 the relapse rate was 21% (N.=12) in group A and 40% (N.=23) (P=0.0309).. In this series of 115 adults with seborrheic dermatitis, patients treated with a topical containing TLR-Regul™ showed a significantly less relapse rate compared with the excipient group (P<0.05). TLR modulation could represent a new therapeutic approach in the prevention of seborrheic dermatitis relapses.

Topics: Administration, Cutaneous; Adult; Aged; Aged, 80 and over; Apiaceae; Dermatitis, Seborrheic; Dermatologic Agents; Double-Blind Method; Erythema; Female; Humans; Interleukin-8; Malassezia; Male; Middle Aged; Ointments; Phytotherapy; Plant Extracts; Pruritus; Secondary Prevention; Toll-Like Receptor 2; Treatment Outcome

Topics: Erythema; Humans; Interleukin-8; Skin; Skin Diseases; Vasculitis, Leukocytoclastic, Cutaneous

UV radiation from the sun is the most common environmental stressor to damage the skin. It is now well established that photodamaged skin manifests signs of mild but chronic inflammation, termed as "inflammaging." Thus, there is an urgent need for anti-inflammatory regimes that can limit the damage caused by inflammation.. This study aimed to evaluate the possible palliative effects of a new topical nanoemulsion formulation containing tocotrienol-rich fraction (TRF) on UV-induced inflammation (erythema) of human skin.. An in vitro model was used to demonstrate the ability of TRF to alleviate photodamage via attenuation of UV-induced oxidative stress and inflammation. Two ex vivo models (skin antioxidative potential and radical sun protection factor) were used to determine the efficacy of different formulations of TRF on the skin. A UV-induced erythema protection test in 20 subjects was conducted.. In vitro studies involving HaCaT keratinocytes revealed that TRF possesses marked anti-inflammatory properties, as indicated by the attenuation of UV-induced upregulation of pro-inflammatory cytokines. A 1% TRF formulation was found to be more effective in enhancing the endogenous antioxidative protection of skin compared to 1% TRF in medium chain triglycerides because of its higher penetration kinetic profile. The clinical study showed that formulated TRF was effective in reducing skin redness after UV irradiation as early as after 6 hours of application. A significant depigmentation was also observed in TRF treatment subjects.. TRF may serve as an anti-inflammatory compound that is safe to be applied daily to protect the skin from UV-induced inflammaging.

Topics: Adult; Animals; Antioxidants; Cell Line; Cell Survival; Cyclooxygenase 2; Deoxyadenosines; Emulsions; Erythema; Humans; Hypopigmentation; Interleukin-6; Interleukin-8; Keratinocytes; Middle Aged; Nanostructures; Oxidative Stress; Radiodermatitis; Reactive Oxygen Species; Swine; Tocotrienols; Ultraviolet Rays

Transient receptor potential type 1 (TRPV1) can be activated by ultraviolet (UV) irradiation, and mediates UV-induced matrix metalloproteinase (MMP)-1 and proinflammatory cytokines in keratinocytes. Various chemicals and compounds targeting TRPV1 activation have been developed, but are not in clinical use mostly due to their safety issues.. We aimed to develop a novel TRPV1-targeting peptide to inhibit UV-induced responses in human skin.. We designed and generated a novel TRPV1 inhibitory peptide (TIP) which mimics the specific site in TRPV1 (aa 701-709: Gln-Arg-Ala-Ile-Thr-Ile-Leu-Asp-Thr, QRAITILDT), Thr. TIP effectively inhibited capsaicin-induced calcium influx and TRPV1 activation. Treatment of HaCaT with TIP prevented UV-induced increases of MMP-1 and pro-inflammatory cytokines such as interleukin (IL)-6 and tumor necrosis factor-α. In mouse skin in vivo, TIP inhibited UV-induced skin thickening and prevented UV-induced expression of MMP-13 and MMP-9. Moreover, TIP attenuated UV-induced erythema and the expression of MMP-1, MMP-2, IL-6, and IL-8 in human skin in vivo.. The novel synthetic peptide targeting TRPV1 can ameliorate UV-induced skin responses in vitro and in vivo, providing a promising therapeutic approach against UV-induced inflammation and photoaging.

Topics: Adult; Animals; Back; Biopsy; Calcium; Capsaicin; Cell Line; Collagenases; Disease Models, Animal; Erythema; Female; Healthy Volunteers; Humans; Interleukin-6; Interleukin-8; Keratinocytes; Male; Mice; Mice, Hairless; Peptides; Phosphorylation; Skin; Skin Aging; Threonine; TRPV Cation Channels; Tumor Necrosis Factor-alpha; Ultraviolet Rays

Post-inflammatory erythema is a common result of acne inflammation and is cosmetically unacceptable without effective treatment. Fractional microneedling radiofrequency (FMR) has potential for treatment of post-inflammatory erythema. The aim of this study was to evaluate the efficacy and safety of this treatment. A retrospective chart review was undertaken of 25 patients treated with 2 sessions of radiofrequency at 4-week intervals and 27 patients treated with oral antibiotics and/or topical agents. Efficacy was assessed through an investigator's global assessment of photographs, and the analysis of erythema with image analysis software and photometric devices. Histological changes resulting from the treatment were evaluated by skin biopsy. FMR treatment resulted in significant improvements in erythema with no severe adverse effects. Histological study revealed a reduction in vascular markers and inflammation. FMR is a safe and effective treatment for post-inflammatory erythema, with potential anti-inflammatory and anti-angiogenetic properties.

Topics: Acne Vulgaris; Biopsy; Equipment Design; Erythema; Female; Humans; Immunohistochemistry; Inflammation Mediators; Interleukin-8; Male; Needles; NF-kappa B; Patient Satisfaction; Pulsed Radiofrequency Treatment; Radio Waves; Retrospective Studies; Skin; Time Factors; Treatment Outcome; Vascular Endothelial Growth Factor A; Young Adult

An effective treatment strategy for acne vulgaris is the reduction of Propionibacterium acnes in the skin. The Helicobacter pylori-derived synthetic antimicrobial peptide HPA3NT3 is a customized α-helical cationic peptide with antibacterial and anti-inflammatory activity.. To examine the role of HPA3NT3 as a treatment against P. acnes-induced skin inflammation.. Morphological alteration of individual P. acnes cells by HPA3NT3 was visualized by scanning electron microscopy. Modulation by HPA3NT3 of a number of P. acnes-induced innate immune responses was analysed in vitro using cultured normal human keratinocytes (HKs), and in vivo using the ICR mouse, a well-established model for P. acnes-induced skin inflammation.. The minimum inhibitory concentration of HPA3NT3 against P. acnes was low (0·4 μmol L(-1)). HPA3NT3 showed no cytotoxicity to HK cells at the concentrations used in our in vitro and in vivo studies. Treatment with HPA3NT3 in vitro induced morphological disruptions in P. acnes cells suggestive of a bactericidal effect. HPA3NT3 significantly decreased P. acnes-induced interleukin-8 expression and intracellular calcium mobilization in HK cells by inhibiting P. acnes-activated Toll-like receptor 2-mediated nuclear factor-κB signalling pathways. Intradermal injection of HPA3NT3 in vivo effectively decreased viable P. acnes, as well as erythema, swelling and inflammatory-cell infiltration in ICR mouse ears inoculated with P. acnes.. Our data suggest that HPA3NT3 has potential as a therapeutic agent for acne vulgaris due to its antimicrobial effects on P. acnes and its ability to block P. acnes-induced inflammation.

Topics: Animals; Anti-Bacterial Agents; Antimicrobial Cationic Peptides; Calcium; Cells, Cultured; Erythema; Gram-Positive Bacterial Infections; Helicobacter pylori; Humans; Injections, Intradermal; Interleukin-8; Keratinocytes; Mice, Inbred ICR; Microbial Sensitivity Tests; Microscopy, Electron, Scanning; NF-kappa B; Peptide Fragments; Propionibacterium acnes; Ribosomal Proteins; RNA, Messenger; Skin Diseases, Bacterial; Toll-Like Receptor 2

In view of several studies highlighting an observation of an erythematous eruption in the vicinity of or distant from the lesion in melanoma patients (The Brenner sign), this study sought to assess whether this phenomenon might be related to the blood level of cytokines IL-6 and IL-8.. Sera specimens obtained from 27 patients with melanoma, of which 15 had erythematous eruptions and 12 did not, were studied by immunohistochemistry for the expression of IL-6 and IL-8.. IL-6 was detected in all melanoma patients in both groups. The mean level of IL-6 in the redness group (2.41 pg/L) was significantly higher than in the group without redness (1.25 pg/L). IL-8 was detected in all 27 melanoma patients in the two groups. The serum level was less than 5 pg/L in only 1 patient (6.7%) in the redness group, and in 6 patients (50%) in the group without redness, a statistically significant difference.. The Brenner sign appears to reflect a more advanced disease and herald a poor prognosis according to its correlation with the IL-8 and IL-6 blood level. However, in view of the biphasic effect of IL-8 level on tumor progression, and IL-6's ability to inhibit early stage melanoma, redness in melanoma patients could be a sign of a better prognosis of the melanoma.

Topics: Erythema; Humans; Immunohistochemistry; Interleukin-6; Interleukin-8; Melanoma

Little is known about cytokines involved in chronic irritant contact dermatitis. Individual cytokine profiles might explain at least part of the differences in the individual response to irritation. Our objective was to investigate the relation between baseline stratum corneum (SC) cytokine levels and the skin response to a single and a repeated irritation test. This study also aimed to determine changes in SC cytokine levels after repeated irritation. Transepidermal water loss (TEWL) and erythema were measured in 20 volunteers after single 24-hr exposure to 1% sodium lauryl sulfate (SLS), and during and after repeated exposure to 0.1% SLS over a 3-week period. SC cytokine levels were measured from an unexposed skin site and from the repeatedly exposed site. Interleukin (IL)-1alpha decreased by 30% after repeated exposure, while IL-1RA increased 10-fold and IL-8 increased fourfold. Baseline IL-1RA and IL-8 values were predictors of TEWL and erythema after single exposure (r = 0.55-0.61). 6 subjects showed barrier recovery during repeated exposure. Baseline IL-1RA and IL-8 levels are likely to be indicators of higher skin irritability after single exposure to SLS. Barrier repair in some of the subjects might explain the lack of agreement between the TEWL response after single and repeated irritation.

Topics: Adult; Body Water; Cytokines; Dermatitis, Irritant; Epidermis; Erythema; Female; Humans; Hypersensitivity, Immediate; Interleukin 1 Receptor Antagonist Protein; Interleukin-1; Interleukin-8; Irritants; Male; Sialoglycoproteins; Sodium Dodecyl Sulfate

Peroxisome proliferator-activated receptors (PPAR) are members of a nuclear receptor superfamily, which were initially described in the context of fatty acid degradation and adipocyte differentiation. In this study we tested the hypothesis that peroxisome proliferator-activated receptor activation also controls inflammation. In an in vitro model with human keratinocytes inflammation was mimicked by irradiation with ultraviolet B light (150 mJ per cm(2)). Activators for PPAR-alpha (WY-14,643, clofibrate) were shown to reverse ultraviolet-B-light-mediated expression of inflammatory cytokines (interleukin-6, interleukin-8). An activator preferentially for PPAR-beta (bezafibrate) did not show prominent effects on interleukin-6 and interleukin-8 expression. The anti-inflammatory action of WY-14,643 on skin cells was further demonstrated by in vivo testings in which topically applied WY-14,643 markedly increased the minimal erythema dose in ultraviolet-B-irradiated skin. Additionally, it was shown that ultraviolet B irradiation led to a decrease of all three peroxisome proliferator-activated receptor subsets at the mRNA level. Also transactivation of peroxisome proliferator response element was attenuated by ultraviolet B irradiation. The downregulation of peroxisome proliferator-activated receptors by ultraviolet B irradiation provides a possible mechanism that leads to exaggerated and prolonged inflammation. This work suggests the possibility of PPAR-alpha activators as novel nonsteroidal anti-inflammatory drugs in the topical treatment of common inflammatory skin diseases such as atopic dermatitis, psoriasis, and photodermatitis.

Topics: Cell Division; Cell Line, Transformed; Dermatitis; DNA Primers; Down-Regulation; Erythema; Gene Expression; Humans; Interleukin-6; Interleukin-8; Keratinocytes; Peroxisome Proliferators; Pyrimidines; Receptors, Cytoplasmic and Nuclear; Response Elements; Skin; Transcription Factors; Ultraviolet Rays

Candidiasis is the most commonly encountered opportunistic infection among HIV-positive subjects. The purpose of this study was to assess specific keratinocyte immune parameters in the pseudomembranous and erythematous forms of HIV-associated oral candidiasis.. This collaborative study from three centers analyzed 25 HIV-positive and 10 HIV-negative subjects with either pseudomembranous or erythematous candidiasis. Oral biopsy specimens from lesional tissues were procured, and histopathologic features were correlated with immunohistochemical and in situ hybridization investigations for the expression of interleukin 1 alpha, interleukin 8, antimicrobial calprotectin, lymphocyte populations, and Candida antigen.. Both pseudomembranous and erythematous candidiasis among HIV-infected subjects showed a mild interface lymphocytic mucositis with the presence of neutrophilic subcorneal abscesses in the latter. Erythematous candidiasis cases that failed to show surface mycelia, did yield positive results for Candida antigens in the parakeratinized layer. The expression of inflammatory chemokines were positive in all groups and calprotectin appeared to serve as a keratinocyte barrier to hyphal penetration.. The erythematous form of candidiasis is often devoid of hyphae yet the presence of Candida antigens in the surface epithelium implicates an immune or allergic process. The intactness of chemokines and antimicrobial calprotectin in keratinocytes may explain why disseminated candidiasis is rarely encountered in HIV-infected patients.

Topics: AIDS-Related Opportunistic Infections; Antigens, Fungal; Antigens, Surface; Calcium-Binding Proteins; Candida; Candidiasis, Oral; Chemokines; Erythema; Gene Expression Regulation; Gene Expression Regulation, Fungal; HIV Seronegativity; HIV Seropositivity; Humans; Hypersensitivity; Immunohistochemistry; In Situ Hybridization; Interleukin-1; Interleukin-8; Keratinocytes; Leukocyte L1 Antigen Complex; Lymphocytes; Mouth Mucosa; Neural Cell Adhesion Molecules; Neutrophils; Stomatitis