Reduced IL-1Ra/IL-1 ratio in ultraviolet B-exposed skin of patients with polymorphic light eruption

Abstract:  Polymorphic light eruption (PLE) is a putative delayed-type allergic reaction to (solar) ultraviolet (UV) exposure. Inadequate immune suppression after UVB-induced sunburn appears to be associated with reduced trafficking of Langerhans cells (LCs) out of and neutrophils into the epidermis of patients sensitive to UVB provocation of PLE. Therefore, we investigated whether pro-inflammatory and chemotactic cytokines are differentially expressed in UVB-irradiated skin of UVB-provocable PLE patients ( n  = 6) and age- and gender-matched healthy controls ( n  = 6). Interstitial interleukin-1α (IL-1α), IL-1β, IL-1Ra, IL-4, IL-8, tumor necrosis factor-α (TNF-α), macrophage inflammatory protein 1-α (MIP-1α), MIP-1β and monocyte chemotactic protein-1 (MCP-1) were measured in suction blister fluid raised 16 h after exposure to 0, three and six minimal erythemal UVB doses. In unirradiated skin, the IL-1Ra levels were significantly lower in the PLE patients than in controls ( P  < 0.05). IL-8 and TNF-α levels increased strongly upon UVB irradiation in both groups. No differential shifts in cytokine profiles were found that could explain a reduced trafficking of Langerhans cells and neutrophils in PLE patients. Dose-trend analyses showed that UVB irradiation caused significant increases in IL-1α in both groups, and that the levels of IL-1α and IL-1β were on average twofold higher in the PLE group ( P  = 0.03 and P  = 0.004, respectively.). Accordingly, the ratios of IL-1Ra over IL-1α and over IL-1β were overall lower in the skin of PLE patients ( P  = 0.015 and P  < 0.001, respectively.). This shift in cytokines in UVB-irradiated skin of PLE patients reveals an amplified early pro-inflammatory cytokine response, which may contribute to the allergic reaction to UVB radiation.