Suppressed alloantigen presentation, increased TNF-alpha, IL-1, IL-1Ra, IL-10, and modulation of TNF-R in UV-irradiated human skin.
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.
Barr
R M
RM
St John's Institute of Dermatology, Guy's, King's, and St Thomas' School of Medicine, King's College London, St Thomas' Hospital, London, UK.
Walker
S L
SL
Tsang
W
W
Harrison
G I
GI
Ettehadi
P
P
Greaves
M W
MW
Young
A R
AR
D000293:Adolescent; D000328:Adult; D015703:Antigens, CD / Q000378:metabolism; D004307:Dose-Response Relationship, Radiation; D015536:Down-Regulation; D005122:Exudates and Transudates / Q000378:metabolism; D005260:Female; D006801:Humans; D053590:Interleukin 1 Receptor Antagonist Protein; D007375:Interleukin-1 / Q000378:metabolism; D016753:Interleukin-10 / Q000378:metabolism; D018664:Interleukin-12 / Q000378:metabolism; D007519:Isoantigens / Q000378:metabolism*; D008297:Male; D008875:Middle Aged; D018124:Receptors, Tumor Necrosis Factor / Q000378:metabolism*; D047888:Receptors, Tumor Necrosis Factor, Type I; D047889:Receptors, Tumor Necrosis Factor, Type II; D012795:Sialoglycoproteins / Q000378:metabolism*; D012867:Skin / Q000276:immunology* / Q000528:radiation effects*; D013997:Time Factors; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism*; D014466:Ultraviolet Rays
D015703:Antigens, CD; C507763:IL1RN protein, human; C507764:Il1rn protein, mouse; D053590:Interleukin 1 Receptor Antagonist Protein; D007375:Interleukin-1; D007519:Isoantigens; D018124:Receptors, Tumor Necrosis Factor; D047888:Receptors, Tumor Necrosis Factor, Type I; D047889:Receptors, Tumor Necrosis Factor, Type II; D012795:Sialoglycoproteins; D014409:Tumor Necrosis Factor-alpha; D016753:Interleukin-10; D018664:Interleukin-12