Sensitivity to sunburn is associated with susceptibility to ultraviolet radiation-induced suppression of cutaneous cell-mediated immunity

Abstract

Skin cancer incidence is highest in white-skinned people. Within this group, skin types I/II (sun sensitive/tan poorly) are at greater risk than skin types III/IV (sun tolerant/tan well). Studies in mice demonstrate that ultraviolet radiation (UVR)-induced suppression of cell-mediated immune function plays an important role in the development of skin cancer and induces a susceptibility to infectious disease. A similar role is suspected in humans, but we lack quantitative human data to make risk assessments of ambient solar exposure on human health. This study demonstrates that ambient levels of solar UVR, typically experienced within 1 h of exposure to noonday summer sunlight, can suppress contact hypersensitivity (CHS) responses in healthy white-skinned humans in vivo (n = 93). There was a linear relationship between increase in erythema and suppression of CHS (P < 0.001), and a moderate sunburn (two minimal erythema doses [2 MED]) was sufficient to suppress CHS in all volunteers by 93%. However, a single suberythemal exposure of either 0.25 or 0.5 MED suppressed CHS responses by 50 and 80%, respectively, in skin types I/II, whereas 1 MED only suppressed CHS by 40% in skin types III/IV. The two- to threefold greater sensitivity of skin types I/II for a given level of sunburn may play a role in their greater sensitivity to skin cancer.

Figure 1

SSR dose–response curves for erythema. Skin types I/II (○) were more sensitive to sunburn/erythema than skin types III/IV (•). The dose of UVR required to induce a just visible reddening of the skin (MED) was 3.2 and 5.5 J.cm⁻², respectively (a). If the same data are expressed as multiples of MED rather than physical dose, the two dose–response curves are comparable, but skin types I/II still have a small (below the visual threshold) but significantly higher erythema response than skin types III/IV (P < 0.002) (b).

Figure 1

SSR dose–response curves for erythema. Skin types I/II (○) were more sensitive to sunburn/erythema than skin types III/IV (•). The dose of UVR required to induce a just visible reddening of the skin (MED) was 3.2 and 5.5 J.cm⁻², respectively (a). If the same data are expressed as multiples of MED rather than physical dose, the two dose–response curves are comparable, but skin types I/II still have a small (below the visual threshold) but significantly higher erythema response than skin types III/IV (P < 0.002) (b).

Figure 3

Sunburn is not a useful indicator of immunosuppression in skin types I/II. Skin types I/II (○) were suppressed with doses of SSR that were below the visual threshold for erythema (1 MED). In contrast, skin types III/IV (•) were suppressed with erythemogenic doses of SSR. All skin types were suppressed with a moderate sunburn (2 MED).

Figure 2

Skin types I/II are more susceptible to UVR-induced immunosuppression than skin types III/IV. Analysis of individual (○, skin type I/II; •, skin type III/IV) and mean (▵, skin type I/II; ▴, skin type III/IV) slopes for CHS response shows that SSR exposure induced a highly significant dose-dependent suppression of cell-mediated immunity in all skin types (P < 0.001). CHS responses of skin types I/II were 5.3-fold lower than those of skin types III/IV throughout the dose range studied (P < 0.001; 95% CI 2.9–9.6).