No / High personal UVR doses can be gained during leisure activities, causing intense self-resolving inflammation (sunburn) of unprotected skin. UVR activates release of membrane fatty acids and upregulates their metabolism by cyclooxygenases (COX) and lipoxygenases (LOX) to different eicosanoids. While COX-derived prostaglandin (PG)E2 is a potent mediator of sunburn vasodilatation, LOX-derived 15-hydroxyeicosatetraenoic acid (HETE) and its lipoxin metabolites may contribute to sunburn limitation. We explored the relationships between expression of these lipid mediators and the clinical and histological outcomes, comparing responses of individuals prone and more resistant to sunburn. An acute UVR exposure of 12 SED (standard erythema dose) was applied to buttock skin of 32 white Caucasians (n = 16 phototype I/II, n = 16 phototype III/IV), and over the subsequent 72 h assessments were made of skin erythema, immunohistochemical expression of leukocyte markers, COX-2, 12-LOX, 15-LOX and nitric oxide synthase (NOS), and eicosanoid levels by LC/ESI-MS/MS. Evidence of a significant inflammatory response was seen earlier in phototype I/II with regard to expression of erythema (4h, p < 0.001), neutrophil infiltration (24 h, p = 0.01), epidermal COX-2 (24 h, p < 0.05) and 12-LOX (24 h, p < 0.01), and dermal eNOS (24 h, p < 0.05) proteins, although CD3+ lymphocyte infiltration showed an earlier increase in phototype III/IV (24 h, p < 0.05). Although erythema was equivalent at 72 h in both groups, phototype I/II showed higher PGE2 accompanied by elevated 15-HETE, and a strong positive correlation was seen between these mediators (n = 18, r = 0.805, p = 0.0001). Hence anti-inflammatory eicosanoid 15-HETE may temper the pro-inflammatory milieu in sunburn, having greater influence in those prone to sunburn than those more resistant, given the same high UVR exposure conditions. / The Wellcome Trust

No / Background: Skin cancer is a major public health concern, and the majority of cases are caused by solar ultraviolet radiation (UVR) exposure, which suppresses skin immunity. Omega-3 (n−3) PUFAs protect against photoimmunosuppression and skin cancer in mice, but the impact in humans is unknown. Objectives: We hypothesized that EPA-rich n−3 PUFA would abrogate photoimmunosuppression in humans. Therefore, a nutritional study was performed to assess the effect on UVR suppression of cutaneous cell-mediated immunity (CMI) reflected by nickel contact hypersensitivity (CHS). Design: In a double-blind, randomized controlled study, 79 volunteers (nickel-allergic women, 22–60 y old, with phototype I or II) took 5 g n−3 PUFA–containing lipid (70% EPA plus 10% DHA) or a control lipid daily for 3 mo. After supplementation, nickel was applied to 3 skin sites preexposed on 3 consecutive days to 1.9, 3.8, or 7.6 J/cm2 of solar-simulated radiation (SSR) and to 3 unexposed control sites. Nickel CHS responses were quantified after 72 h and the percentage of immunosuppression by SSR was calculated. Erythrocyte [red blood cell (RBC)] EPA was measured by using gas chromatography. Results: SSR dose-related suppression of the nickel CHS response was observed in both groups. Photoimmunosuppression appeared less in the n−3 PUFA group than in the control group (not statistically significant [mean difference (95% CI): 6.9% (−2.1%, 15.9%)]). The difference was greatest at 3.8 J/cm2 SSR [mean difference: 11% (95% CI: 0.5%, 21.4%)]. Postsupplementation RBC EPA was 4-fold higher in the n−3 PUFA group than in the control group (mean difference: 2.69% (95% CI: 2.23%, 3.14%), which confirmed the EPA bioavailability. Conclusion: Oral n−3 PUFAs appear to abrogate photoimmunosuppression in human skin, providing additional support for their chemopreventive role; verification of study findings is required.