Dose response for UV-induced immune suppression in people of color: differences based on erythemal reactivity rather than skin pigmentation.

Ultraviolet radiation (UVR) is known to suppress immune responses in human subjects. The purpose of this study was to develop dose responses across a broad range of skin pigmentation in order to facilitate risk assessment. UVR was administered using FS 20 bulbs. Skin pigmentation and UVR sensitivity were evaluated using Fitzpatrick classifications, minimal erythemal dose (MED), slope of the erythemal dose response curve (sED), baseline pigmentation and tanning response. To assess immune responses dinitrochlorobenzene (DNCB) was applied to irradiated buttock skin 72 h after irradiation. Two weeks later DNCB was applied to the inside upper arm. Skin thickness was measured before and after challenge. Dose response was modeled (to obtain a regression line) for the entire group of 185 subjects. With the exception of sED none of the above-mentioned pigmentation indicators contributed significantly to variability around the regression line. Thus, differences in sensitivity for multiple skin types based on Fitzpatrick classification or MED were not observed. However, differences in immune sensitivity to UVR were detected between subjects with steep erythemal dose response curves and those with moderate or flat responses. For subjects with steep erythemal responses the dose calculated to suppress the immune response by 50% was 114 mJ/cm2. This group included individuals with Fitzpatrick skin types I-V, MED for these subjects ranged from 30 to 80 mJ/cm2. The 50% suppression dose for subjects with weak or no erythemal response could not be computed (the dose response was flat). This resistant group included subjects with skin types IV-VI and MED for these subjects ranged from 41 to > 105 mJ/cm2. This study provides a human dose response for UVR suppression of contact sensitivity that will be useful in risk assessment. It is the first study to provide this information using the FS sun lamp and is the first study to include people of color. The sED appears to be a new variable for identifying sensitive subjects at risk of UVR-induced immune suppression.

UVA II exposure of human skin results in decreased immunization capacity, increased induction of tolerance and a unique pattern of epidermal antigen-presenting cell alteration.

The risks incurred from increased exposure to UVA II (320-340 nm) (i.e. during sunscreen use and extended outdoor exposure, tanning parlors) are not well understood. Therefore, we explored the effects of UVA II on skin immune responses in humans. After a single local exposure (4 minimum erythemal dose [MED]) using a xenon are lamp filtered with a narrow bandpass filter (335 +/- 5 nm full width at half maximum), individuals were contact-sensitized with dinitrochlorobenzene (DNCB) through a UVA II exposure site or through normal skin. UVA II induced a marked decrease in the magnitude of skin immune responses (P < 0.0001). The UVA II group had only 29% successful sensitizations, as compared to 83% in the control group. The percentage of individuals who remained tolerant to DNCB after two sensitizations was 23.6% for the UVA II-exposed group, as compared to 3.8% in the controls (P = 0.006). UVA II also uniquely altered the type of antigen-presenting cells present in the epidermis. Human leukocyte antigen (HLA)-DR+ cells in control epidermal cell suspensions (C-EC) comprised a single, homogeneous population of Langerhans cells (LC) with the phenotype: CD1ahi DRmid CD11b CD36 (1.5 +/- 0.3% of EC). UVA II irradiation reduced the number of such LC to 0.6 +/- 0.2% of EC. Although cells expressing the macrophage phenotype: CD1a- DRhi CD11b+ CD36+ were increased in UVA II skin, relative to C-EC, these comprised only 10.1 +/- 6.1% of the DR+ cells, which is less than that after UVB exposure. Also distinct from UVB, a third population was found in UVA II-EC, which exhibited a novel phenotype: CD1a+ DR+ CD36+ CD11b+; these comprised 11.1 +/- 6.9% of the DR+ UVA II-EC. In conclusion, despite the above differences in infiltrating DR+ cells, both UVB and UVA II reduce the skin's ability to support contact sensitization, induce active suppression (tolerance) and induce a reduction in LC.

Photoreversal of the ultraviolet radiation-induced disappearance of ATPase-positive Langerhans cells in the epidermis of Monodelphis domestica.

The present study was undertaken to explore the possible causes of ultraviolet radiation (UVR)-induced disappearance of ATPase-positive, epidermal Langerhans cells (LC). Monodelphis domestica was used because it has the capacity for photoreactivation of UVR-induced pyrimidine dimers in epidermal DNA. Single, 330 J/m2 (ears) or 500 J/m2 (back) UVR exposures (FS-40 sunlamps) reduced the numbers of ATPase-positive epidermal LC in M. domestica ears to approximately 15% of those in unirradiated ears and approximately 37% of those in unirradiated dorsal skin. Immediate 90-minute exposures to photoreactivating light (PRL, 320-400 nm) post-UVR reversed the effects of UVR, resulting in ATPase-positive LC numbers not being significantly different from controls. Exposure to PRL immediately preceeding UVR did not prevent ATPase-positive LC disappearance. The photoreactivation of UVR-induced ATPase-positive LC disappearance indicates that DNA damage (pyrimidine dimers) is involved in the loss of ATPase-positive LC.

P-aminobenzoic acid as a sunscreen and its behaviour on the skin.

Synopsis PABA (p-aminobenzoic acid), a highly regarded sunscreening agent, has recently been shown to exhibit different absorption characteristics when applied to excised hairless mouse epidermis than when in dilute alcoholic solution. In the present study the cause of the differences was investigated. The results show that at normal application amounts, considerable quantities of randomly dispersed PABA micro-crystals exist on the skin surface. The forward scattering spectrum of PABA on skin resembled more closely that of micro-crystalline aggregates than that of PABA in solution.

Performance of six sunscreen formulations on human skin: a comparison.

Indoor and outdoor tests were performed on human volunteers to determine the protection offered by six commercially available products containing single sunscreen ingredients and combinations of ingredients. Indoor solar simulator studies were performed to determine the inherent efficacy of each product, including use of a whirlpool treatment to evaluate the resistance of each product to wash off. The outdoor study included a ten-minute swimming period followed by sunlight exposure. In all tests, the combination of 7% octyl-dimethyl p-aminobenzoic acid ester and 3% oxybenzone was substantially more effective in protecting against sunburn than any other formula tested, including 5% p-aminobenzoic acid (PABA).