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Immunologic Protection Afforded by Sunscreens Beyond Designated Sun Protection Factors?
LETTERS TO THE EDITOR
Immunologic Protection Afforded by Sunscreens Beyond Designated Sun Protection Factors? different individuals. An individual’s MED depends heavily on skin type; in contrast, there appears to be little correlation between skin type and MISD, based on in vivo measurement of the contact hypersensitivity response (Vermeer et al, 1991). Similarly, exposing human subjects to 1.25 MED of solar simulated UV produced a large variation in depletion of epidermal Langerhans cells (0–64%) 24 h later, and no correlation was found between MED and depletion of Langerhans cells in individuals (Alcalay et al, 1989). As Davenport et al (1997) point out, sensitivity to UV-induced immune suppression seems to be under genetic control; however, the relevant genes appear to be independent of those controlling skin type (Streilein et al, 1994). Thus, MED and MISD are independent variables whose relationship in a particular individual is completely unpredictable. Therefore, the most objective approach for assessing a sunscreen’s immunoprotective capacity is to determine an MISD or ISD50 for the particular immunologic assay and to calculate an IPF using the conventional formula. Clearly, more information is needed on the variance of MISD among individuals, the action spectra for various forms of immune suppression, how the in vitro alloantigen presentation assay relates to an immune response in vivo, and whether the MISD from in vitro irradiation reflects the MISD obtained following in vivo irradiation. Although the study by Davenport et al (1997) represents an important step in developing an in vitro assay for immune protection, much remains to be done before the significance of this assay for photoprotection of humans in vivo becomes clear.
To the Editor: In the June issue of the Journal of Investigative Dermatology, Davenport et al (1997) reported on the capacity of various sunscreens to protect against ultraviolet radiation (UVR)-induced suppression of the alloantigenpresenting activity of epidermal cells. They used a system in which human skin explants were exposed in culture to graded doses of solar simulated UVR, and epidermal cells were then isolated and used as stimulators in a mixed epidermal cell-leukocyte reaction. Five different sunscreens with sun protection factors (SPF) ranging from 3.5 to 5.7 afforded full immune protection up to 8 minimal erythema dose (MED) equivalents of UVR. The results of this study are important because of the controversy surrounding the potential of sunscreens to provide immune protection (Bestak et al, 1995; Granstein, 1995; Roberts and Beasley, 1995; Whitemore and Morison, 1995; Wolf and Kripke, 1996; Walker and Young, 1997) and the need to develop a relevant, standardized test for assessing the immune protective capacity of sunscreens. Unfortunately, however, the authors did not determine immune protection factors for the sunscreens and therefore concluded incorrectly that all the sunscreens protected epidermal alloantigenpresenting function beyond their SPF value. The conventional mode of SPF determination is to divide the minimum UV dose eliciting a detectable response in sunscreenprotected skin by the minimum dose eliciting a response in unprotected skin. In this study, a minimum immunosuppressive dose (MISD) was not determined, which would have allowed calculation of an immunosuppression protection factor (IPF) based on a minimally effective UV dose. None the less, the data presented in Fig 3 and Table I of the paper permit estimation of the dose required for 50% immune suppression (ISD50), which has been used in other studies (Roberts and Beasley, 1995) to derive an IPF. Dividing the ISD50 obtained with sunscreens by the ISD50 obtained without sunscreens reveals that, measured in this way, the IPF are only around 2.4. Thus, the conclusion that ‘‘sunscreen agents all protect epidermal alloantigenpresenting function beyond their designated SPF values’’ (Davenport et al, 1997) is incorrect. In spite of the erroneous conclusion, this model represents an important advance in that it employs human, rather than murine, skin, a light source that approximates the UV content of natural sunlight, and a range of UV doses, rather than a single dose. It also serves to illustrate the difficulties inherent in attempting to relate a sunscreen’s IPF to its SPF. One way would be to ask whether a sunscreen with a particular SPF will protect against both immune suppression and erythema at a given dose of solar UVR, which seems to be the approach taken by Davenport et al (1997). The problem with this approach is that the IPF and SPF both depend critically on their respective action spectra, and although that for erythema is well defined, there is little information on action spectra for the various measures of immune suppression in humans. A second problem is that the relationship between MED and MISD is likely to differ greatly in
Peter Wolf Department of Dermatology, Karl Franzens University, Graz, Austria Margaret L. Kripke The University of Texas, M.D. Anderson Cancer Center, Houston, Texas, U.S.A. REFERENCES Alcalay J, Goldberg LH, Kripke ML, Wolf JE Jr: The sensitivity of Langerhans cells to simulated solar radiation in basal cell carcinoma patients. J Invest Dermatol 93: 746–750, 1989 Bestak R, Barnetson RSC, Nearn MR, Halliday GM: Sunscreen protection of contact hypersensitivity responses from chronic solar-simulated ultraviolet irradiation correlates with the absorption spectrum of the sunscreen. J Invest Dermatol 105: 345–351, 1995 Davenport V, Morris JF, Chu AC: Immunologic protection afforded by sunscreens in vitro. J Invest Dermatol 108:859–863, 1997 Granstein RD: Evidence that sunscreens prevent UV radiation-induced immunosuppression in humans. Arch Dermatol 131:1201–1204, 1995 Roberts LK, Beasley DG: Commercial sunscreen lotions prevent ultraviolet-radiationinduced immune suppression of contact hypersensitivity. J Invest Dermatol 105: 339–344, 1995 Streilein JW, Taylor JR, Vincek V, Kurimoto I, Shimizu T, Tie C, Golomb C: Immune surveillance and sunlight-induced skin cancer. Immunol Today 15:174–179, 1994 Vermeer M, Schmieder GJ, Yoshikawa T, van den Berg J-W, Metzman MS, Taylor JR, Streilein JW: Effects of ultraviolet B light on cutaneous immune responses of humans with deeply pigmented skin. J Invest Dermatol 97:729–734, 1991 Walker SL, Young AR: Sunscreens offer the same UVB protection factors for inflammation and immunosuppression in the mouse. J Invest Dermatol 108:133–138, 1997 Whitemore SE, Morison WL: Prevention of UVB-induced immunosuppression in humans by a high sun protection factor sunscreen. Arch Dermatol 131:1128–1133, 1995 Wolf P, Kripke ML: Sunscreens and immunosuppression. J Invest Dermatol 106: 1152–1153, 1996
Manuscript received September 3, 1997; accepted for publication November 19, 1997. Abbreviations: IPF, immunosuppression protection factor; ISD50, 50% immune suppression; MISD, minimum immunosuppressive dose; SPF, sun protection factor.
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0022-202X/98/$10.50 Copyright © 1998 by The Society for Investigative Dermatology, Inc.
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Immunologic Protection Afforded by Sunscreens Beyond Designated Sun Protection Factors? different individuals. An individual’s MED depends heavily on skin type; in contrast, there appears to be little correlation between skin type and MISD, based on in vivo measurement of the contact hypersensitivity response (Vermeer et al, 1991). Similarly, exposing human subjects to 1.25 MED of solar simulated UV produced a large variation in depletion of epidermal Langerhans cells (0–64%) 24 h later, and no correlation was found between MED and depletion of Langerhans cells in individuals (Alcalay et al, 1989). As Davenport et al (1997) point out, sensitivity to UV-induced immune suppression seems to be under genetic control; however, the relevant genes appear to be independent of those controlling skin type (Streilein et al, 1994). Thus, MED and MISD are independent variables whose relationship in a particular individual is completely unpredictable. Therefore, the most objective approach for assessing a sunscreen’s immunoprotective capacity is to determine an MISD or ISD50 for the particular immunologic assay and to calculate an IPF using the conventional formula. Clearly, more information is needed on the variance of MISD among individuals, the action spectra for various forms of immune suppression, how the in vitro alloantigen presentation assay relates to an immune response in vivo, and whether the MISD from in vitro irradiation reflects the MISD obtained following in vivo irradiation. Although the study by Davenport et al (1997) represents an important step in developing an in vitro assay for immune protection, much remains to be done before the significance of this assay for photoprotection of humans in vivo becomes clear.
To the Editor: In the June issue of the Journal of Investigative Dermatology, Davenport et al (1997) reported on the capacity of various sunscreens to protect against ultraviolet radiation (UVR)-induced suppression of the alloantigenpresenting activity of epidermal cells. They used a system in which human skin explants were exposed in culture to graded doses of solar simulated UVR, and epidermal cells were then isolated and used as stimulators in a mixed epidermal cell-leukocyte reaction. Five different sunscreens with sun protection factors (SPF) ranging from 3.5 to 5.7 afforded full immune protection up to 8 minimal erythema dose (MED) equivalents of UVR. The results of this study are important because of the controversy surrounding the potential of sunscreens to provide immune protection (Bestak et al, 1995; Granstein, 1995; Roberts and Beasley, 1995; Whitemore and Morison, 1995; Wolf and Kripke, 1996; Walker and Young, 1997) and the need to develop a relevant, standardized test for assessing the immune protective capacity of sunscreens. Unfortunately, however, the authors did not determine immune protection factors for the sunscreens and therefore concluded incorrectly that all the sunscreens protected epidermal alloantigenpresenting function beyond their SPF value. The conventional mode of SPF determination is to divide the minimum UV dose eliciting a detectable response in sunscreenprotected skin by the minimum dose eliciting a response in unprotected skin. In this study, a minimum immunosuppressive dose (MISD) was not determined, which would have allowed calculation of an immunosuppression protection factor (IPF) based on a minimally effective UV dose. None the less, the data presented in Fig 3 and Table I of the paper permit estimation of the dose required for 50% immune suppression (ISD50), which has been used in other studies (Roberts and Beasley, 1995) to derive an IPF. Dividing the ISD50 obtained with sunscreens by the ISD50 obtained without sunscreens reveals that, measured in this way, the IPF are only around 2.4. Thus, the conclusion that ‘‘sunscreen agents all protect epidermal alloantigenpresenting function beyond their designated SPF values’’ (Davenport et al, 1997) is incorrect. In spite of the erroneous conclusion, this model represents an important advance in that it employs human, rather than murine, skin, a light source that approximates the UV content of natural sunlight, and a range of UV doses, rather than a single dose. It also serves to illustrate the difficulties inherent in attempting to relate a sunscreen’s IPF to its SPF. One way would be to ask whether a sunscreen with a particular SPF will protect against both immune suppression and erythema at a given dose of solar UVR, which seems to be the approach taken by Davenport et al (1997). The problem with this approach is that the IPF and SPF both depend critically on their respective action spectra, and although that for erythema is well defined, there is little information on action spectra for the various measures of immune suppression in humans. A second problem is that the relationship between MED and MISD is likely to differ greatly in
Peter Wolf Department of Dermatology, Karl Franzens University, Graz, Austria Margaret L. Kripke The University of Texas, M.D. Anderson Cancer Center, Houston, Texas, U.S.A. REFERENCES Alcalay J, Goldberg LH, Kripke ML, Wolf JE Jr: The sensitivity of Langerhans cells to simulated solar radiation in basal cell carcinoma patients. J Invest Dermatol 93: 746–750, 1989 Bestak R, Barnetson RSC, Nearn MR, Halliday GM: Sunscreen protection of contact hypersensitivity responses from chronic solar-simulated ultraviolet irradiation correlates with the absorption spectrum of the sunscreen. J Invest Dermatol 105: 345–351, 1995 Davenport V, Morris JF, Chu AC: Immunologic protection afforded by sunscreens in vitro. J Invest Dermatol 108:859–863, 1997 Granstein RD: Evidence that sunscreens prevent UV radiation-induced immunosuppression in humans. Arch Dermatol 131:1201–1204, 1995 Roberts LK, Beasley DG: Commercial sunscreen lotions prevent ultraviolet-radiationinduced immune suppression of contact hypersensitivity. J Invest Dermatol 105: 339–344, 1995 Streilein JW, Taylor JR, Vincek V, Kurimoto I, Shimizu T, Tie C, Golomb C: Immune surveillance and sunlight-induced skin cancer. Immunol Today 15:174–179, 1994 Vermeer M, Schmieder GJ, Yoshikawa T, van den Berg J-W, Metzman MS, Taylor JR, Streilein JW: Effects of ultraviolet B light on cutaneous immune responses of humans with deeply pigmented skin. J Invest Dermatol 97:729–734, 1991 Walker SL, Young AR: Sunscreens offer the same UVB protection factors for inflammation and immunosuppression in the mouse. J Invest Dermatol 108:133–138, 1997 Whitemore SE, Morison WL: Prevention of UVB-induced immunosuppression in humans by a high sun protection factor sunscreen. Arch Dermatol 131:1128–1133, 1995 Wolf P, Kripke ML: Sunscreens and immunosuppression. J Invest Dermatol 106: 1152–1153, 1996
Manuscript received September 3, 1997; accepted for publication November 19, 1997. Abbreviations: IPF, immunosuppression protection factor; ISD50, 50% immune suppression; MISD, minimum immunosuppressive dose; SPF, sun protection factor.
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0022-202X/98/$10.50 Copyright © 1998 by The Society for Investigative Dermatology, Inc.
184