Phototherapeutic hardening modulates systemic cytokine levels in patients with polymorphic light eruption

Wolf, Peter; Gruber‐Wackernagel, Alexandra; Rinner, Beate; Griesbacher, Antonia; Eberhard, Katharina; Groselj‐Strele, Andrea; Mayer, Gerlinde; Stauber, Rudolf; Byrne, Scott N.

doi:10.1039/c2pp25187f

Cited by 27 publications

(29 citation statements)

References 62 publications

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“…While previous studies demonstrate that both keratinocytes and fibroblasts can produce proinflammatory cytokines upon stimulation (Ablett et al, 2003; Huleihel et al, 1993; Köck et al, 1990; Mustafa et al, 2000; Urbanski et al, 1990; Wolf et al, 2013), our results further suggest that the skin is likely an important contributor to the age-associated increase in serum inflammatory cytokines. While aged mice display elevated serum amyloid A and TNFα levels, mRNA levels of both amyloid A and TNFα increase only in the aged skin, but not in the liver, a putative source of serum amyloid A (Upragarin et al, 2005).…”

Section: Discussioncontrasting

confidence: 70%

Epidermal Dysfunction Leads to an Age-Associated Increase in Levels of Serum Inflammatory Cytokines

Mauro

Dang

et al. 2017

Journal of Investigative Dermatology

100

117

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Even though elderly populations lack visible or other clinical signs of inflammation, their serum cytokine and C reactive protein levels typically are elevated. However, the origin of age-associated systemic inflammation is unknown. Our previous studies showed that abnormalities in epidermal function provoke cutaneous inflammation, and because intrinsically aged skin displays compromised permeability barrier homeostasis, as well as reduced stratum corneum hydration, we hypothesized here that epidermal dysfunction could contribute to the elevations in serum cytokines in the elderly. Our results show first that acute disruption of the epidermal permeability barrier in young mice led not only to a rapid increase in cutaneous cytokine mRNA expression, but also an increase in serum cytokine levels. Second, cytokine levels in both the skin and serum increased in otherwise normal, aged mice (>12 months). Third, expression of TNFα and amyloid A mRNA levels increased in the epidermis, but not in the liver, in parallel with significant elevations in serum levels of cytokines. Fourth, disruption of the permeability barrier induced similar elevations in epidermal and serum cytokine levels in normal and athymic mice, suggesting the T cells play a negligible role in the elevations in cutaneous and serum inflammatory cytokines induced by epidermal dysfunction. Fifth, correction of epidermal function significantly reduced cytokine levels not only in the skin, but also in the serum of aged mice. Together, these results indicate that the sustained abnormalities in epidermal function in chronologically aged skin contribute to the elevated serum levels of inflammatory cytokines, potentially predisposing the elderly to the subsequent development or exacerbation of chronic inflammatory disorders.

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Section: Discussioncontrasting

confidence: 70%

Epidermal Dysfunction Leads to an Age-Associated Increase in Levels of Serum Inflammatory Cytokines

Mauro

Dang

et al. 2017

Journal of Investigative Dermatology

100

117

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“…Chronologically aged mice, with no clinical evidence of inflammation, exhibit cutaneous functional abnormalities, which are accompanied by elevated levels of certain cytokines in the skin and circulation . Pertinently, disruption of epidermal permeability barrier function by repeated tape‐stripping, and following acute exposure to erythemogenic UV‐B provoke increases in the levels of cutaneous and circulating cytokines, including IL‐1β, IL‐6 and TNFα …”

Section: Discussionmentioning

confidence: 57%

Topical applications of an emollient reduce circulating pro‐inflammatory cytokine levels in chronically aged humans: a pilot clinical study

Mauro

Dang

et al. 2019

Acad Dermatol Venereol

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Background While increased levels of circulating inflammatory cytokines in chronologically aged humans have been linked to the development of ageing‐associated chronic disorders (e.g., cardiovascular disease, type II diabetes, osteoporosis and Alzheimer's disease), approaches that reduce circulating cytokines are not yet available. In chronologically aged mice, we recently demonstrated that epidermal dysfunction largely accounts for age‐associated elevations in circulating cytokine levels, and that improving epidermal function reduced circulating cytokine levels. Objective We performed a pilot study to determine whether improving epidermal function reduces circulating pro‐inflammatory cytokine levels in aged humans. Methods Thirty‐three aged humans were topically treated twice‐daily for 30 days, with ≈ 3 mL of an emollient, previously shown to improve epidermal function, while untreated, aged humans and a cohort of young volunteers served as controls. Changes in epidermal function and levels of three key, age‐related, plasma cytokines (IL‐1β, IL‐6 and TNFα) were measured at baseline and after treatment, using Luminex 200™ system. Results We also found significantly higher baseline levels of IL‐1β, IL‐6 and TNFα in aged vs. young humans (P < 0.001), as previously reported. Topical applications of the barrier repair emollient significantly enhanced epidermal permeability barrier function (P < 0.01) and stratum corneum hydration (P < 0.05). In parallel, circulating levels of IL‐1β and IL‐6 normalized, while TNFα levels declined substantially. Conclusion The results of this preliminary study suggest that a larger clinical trial should be performed to confirm whether improving epidermal function also can reduce circulating pro‐inflammatory cytokine levels in aged humans, while also possibly attenuating the downstream development of chronic inflammatory disorders in the aged humans.

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“…6 The induction of allergic contact sensitization against dinitrochlorobenzene following UV irradiation of the sensitization site was shown to occur significantly more frequently in patients with PLE than in healthy subjects. 11,22 In comparison with controls, we found that TGF-b1 expression in both PLE and CDLE was decreased by > 50%, indicating that both conditions are characterized by similar dysbalances in the number of Tregs and the cytokine network. However, the allergic contact response to dinitrochlorobenzene in previously sensitized patients with PLE and healthy subjects is gradually and equally suppressed by irradiation, also explaining the beneficial effect of UV hardening in patients with PLE.…”

Section: Discussionmentioning

confidence: 78%

“…20 As shown in previous studies, we observed that epidermal Langerhans cells are also significantly diminished in CDLE. [3][4][5]22 In skin lesions of patients with PLE, we have investigated Tregs and immunoregulatory factors such as TGF-b1, IL-10 and RANKL. 21 We observed significantly reduced levels of CD68+ cells in the epidermis of PLE lesions compared with CDLE and controls.…”

Section: Discussionmentioning

confidence: 99%

T regulatory cells and related immunoregulatory factors in polymorphic light eruption following ultraviolet A1 challenge

et al. 2013

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Phototherapeutic hardening modulates systemic cytokine levels in patients with polymorphic light eruption

Cited by 27 publications

References 62 publications

Epidermal Dysfunction Leads to an Age-Associated Increase in Levels of Serum Inflammatory Cytokines

Epidermal Dysfunction Leads to an Age-Associated Increase in Levels of Serum Inflammatory Cytokines

Topical applications of an emollient reduce circulating pro‐inflammatory cytokine levels in chronically aged humans: a pilot clinical study

T regulatory cells and related immunoregulatory factors in polymorphic light eruption following ultraviolet A1 challenge

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