Using an in vivo skin chamber method, we demonstrated increased release of interleukin-1 (IL-1)-like activity at the site of irradiation with 3 times the minimal erythema dose of ultraviolet B (UVB). IL-1-like activity was estimated using the mouse thymocyte amplification assay. UVB-augmented release of IL-1-like activity peaked 1 h after irradiation and levels returned to baseline by 2 h. Release of IL-1-like activity from human skin after exposure to UV radiation may account for some of the local and systemic features of the sunburn response.
"J Invest Dermatol 108:592, 1997 (abstr.) a 300-fold molar excess of IL-1Ra above the sum of IL-1α and IL-1β for both irradiated and unirradiated skin, but other studies suggest that a considerable excess of IL-1Ra is required to inhibit fully the IL-1 activity (Arend et al, 1990). The detection by bioassay of increased IL-1-like activity in abraded UVB-irradiated skin (Murphy et al, 1989) is evidence that IL-1 agonist activity predominates over IL-1Ra in skin exudate. TNF-α induces IL-1Ra and IL-1α release from keratinocytes (Kutsch et al, 1993). "
[Show abstract][Hide abstract] ABSTRACT: Cytokines induced in skin by ultraviolet radiation cause local and systemic immunosuppression. Tumor necrosis factor alpha, interleukin-1, and interleukin-10 are key mediators in the mouse, but less is known about cytokine synthesis and function in ultraviolet-irradiated human skin. We exposed human skin to 3 minimal erythema doses of solar-simulated radiation and raised suction blisters at intervals to 72 h. Alloantigen presentation was suppressed in a mixed epidermal cell-lymphocyte reaction by 69% from 4 to 15 h post-solar-simulated radiation, but recovered to control values by 24 h. Tumor necrosis factor alpha was raised at 4 h after solar-simulated radiation, reached a maximum 8-fold increase at 15 h, then rapidly declined to control values. Interleukin-1alpha and interleukin-1beta were first increased at 15 h, and remained raised to 72 h, although interleukin-1beta declined from its 15 h maximum. Interleukin-10 increased a maximum 2-fold between 15 and 24 h, coincident with recovery of mixed epidermal cell-lymphocyte reaction responses and downregulation of tumor necrosis factor alpha and interleukin-1beta. Solar-simulated radiation differentially affected soluble tumor necrosis factor alpha receptors; soluble tumor necrosis factor-RI was suppressed 33% at 8-15 h whereas soluble tumor necrosis factor-RII increased 2-fold from 15 to 48 h. Interleukin-1 receptor antagonist was raised at all times post-irradiation. Interleukin-12 was not detectable in control or irradiated skin. These kinetics suggest the tumor necrosis factor alpha network has primary importance in ultraviolet-damaged human skin. The small increase in interleukin-10 implies that 3 minimal erythema doses of solar-simulated radiation is the threshold dose for its induction and local, rather than systemic, functions for interleukin-10 in immunosuppression and regulation of other cytokines.
[Show abstract][Hide abstract] ABSTRACT: The objective of these studies was to characterize the IL-1 inhibitory activity present in normal and psoriatic epidermis from clinically stable lesions. Fractionation of normal epidermal cytosol on a molecular sizing column failed to reveal the presence of IL-1 inhibitory bioactivity. However, specific ELISAs indicated that both the IL-1 receptor antagonist (IL-1ra) and IL-1 alpha were present in overlapping peaks. Further fractionation of the normal epidermal cytosol by anion exchange chromatography separated these two molecules, revealing the IL-1 inhibitory bioactivity of the IL-1ra molecule. Similar studies on psoriatic epidermal cytosol indicated the presence of IL-1 inhibitory bioactivity and IL-1ra protein. The IL-1 inhibitory bioactivity of both normal and psoriatic cytosol was neutralized by a mAb specific for IL-1ra. The ratio of IL-1ra to IL-1 alpha proteins was significantly increased in involved psoriatic skin compared with normal skin. By Western blot analysis this IL-1ra was approximately 20 kD, slightly larger than monocyte-derived IL-1ra and equivalent to an intracellular variant of IL-1ra expressed by keratinocytes. Polymerase chain reaction indicated the presence of mRNA for both forms of IL-1ra in normal epidermis, with both forms increased in psoriatic-involved skin. Immunofluorescence studies revealed the IL-1ra protein to be concentrated in the stratum granulosum of normal skin and in the basal-midbasal layers of psoriatic epidermis. These results suggest that the balance between intracellular IL-1ra and IL-1 alpha may be an important influence on keratinocyte growth and/or differentiation, as well as on the inflammatory potential of IL-1 in injured skin.
[Show abstract][Hide abstract] ABSTRACT: 1. The role of nitric oxide synthase and cyclo-oxygenase in the skin blood flow response to ultraviolet light B (u.v.B) irradiation was investigated in the rat in vivo. 2. Local skin blood flow changes were measured in the shaved dorsal skin of anaesthetized male Sprague-Dawley rats with a laser Doppler flow probe. 3. u.v.B irradiation caused delayed onset vasodilation and by 18 h basal blood flow increased by 125 +/- 25% (P < 0.05, n = 12 rats, mean +/- s.e. mean). 4. Indomethacin, 3 nmol per site, NG-nitro-L-arginine methyl ester (L-NAME) 100 nmol per site, but not D-NAME 100 nmol per site, injected locally 17.5 h after u.v.B irradiation abolished the 18 h increase in blood flow. 5. The nitric oxide synthase inhibitor L-NAME, NG-monomethyl-L-arginine (L-NMMA) and canavanine, 10 and 100 nmol per site injected at 17.5 h, suppressed significantly the u.v.B 18 h response in a dose-dependent manner. The order of potency was L-NAME > canavanine = L-NMMA. The effect of L-NAME was reversed partially by the co-injection of an excess of L-arginine. 6. Topical application of the corticosteroid, clobetasol 17-propionate, immediately after irradiation inhibited the 18 h u.v.B response in a dose-dependent manner. 7. The delayed onset microcirculatory vasodilation induced by u.v.B involves both nitric oxide synthase and cyclo-oxygenase in this in vivo model. Topical corticosteroids may attenuate the response by inhibiting both prostaglandin and nitric oxide synthesis pathways.
British Journal of Pharmacology 07/1993; 109(3):802-6. DOI:10.1111/j.1476-5381.1993.tb13645.x · 4.84 Impact Factor
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