Results of photoprovocation and field studies on the efficacy of a novel topically applied antioxidant in polymorphous light eruption.

BACKGROUND: UVA-induced photooxidation is considered to play an essential role in the pathogenesis of polymorphous light eruption (PLE), and topical pretreatment of skin with alpha-glucosylrutin (AGR), a potent plant-derived antioxidant, has been shown to significantly suppress photoprovoked PLE eruption. AIM: In order to further elucidate the optimum pretreatment regimen and to investigate the efficacy and skin compatibility of topical preparations containing AGR under field conditions, two controlled clinical studies were conducted in PLE patients. METHODS: In the first study, photoprovocation of PLE was performed in 20 patients, using UVA irradiation (4 x 60-100 J/cm(2)), applied to four test sites at the individual areas of predilection. One site served as an untreated control. The remaining three sites received treatment with a SPF 15 sunscreen containing 0.25% AGR (Eucerin Gel Cream Phase 2) 30 minutes before irradiation. Two of these sites were additionally pretreated with the corresponding AGR-containing vehicle (Eucerin Gel Cream Phase 1) twice daily for 3 and 7 days, respectively. The second study was conducted as a controlled in-use-test in patients with PLE (n = 27) or acne aestivalis (n = 3), who had suffered from the disease during their last year's vacation. They were educated to apply the pre-sun preparation to the formerly affected skin areas twice daily for 1 week before their planned vacation and to use the SPF 15 sunscreen 30 minutes before each vacation sun exposure. Symptoms were recorded in patients' diaries throughout the vacation and documented by a physician after their return. RESULTS: In the first study, protection of skin with the SPF 15 sunscreen alone led to a significant prevention of PLE symptoms, especially itch, compared with the control area. Pretreatment further reduced the severity of PLE significantly and led to total prevention in 19 patients. In the second study, whereas 92.6% had reported severe and 7.4% mild PLE in the last year, there were currently only 7.4% severe cases, with 25.9% mild and 29.6% questionable cases; 37% had no symptoms at all. Also, two out of three acne aestivalis patients had diminished symptoms after treatment. CONCLUSION: The results confirm the prophylactic efficacy of the antioxidant AGR in PLE, applied as SPF 15 sunscreen alone or additionally to pretreatment with a corresponding pre-sun preparation, and also show an effect in acne aestivalis patients.

Cytokine RANTES released by thrombin-stimulated platelets is a potent attractant for human eosinophils.

Thrombin stimulation of human platelets results in the release of a preformed proteinaceous human eosinophil (Eo)-chemotactic activity. By the use of different high-performance liquid chromatography techniques, two Eo-chemotactic polypeptides (EoCPs), tentatively termed EoCP-1 and EoCP-2, were purified to homogeneity. Upon SDS-PAGE analysis, these chemotaxins showed molecular masses near 8 kD. NH2-terminal amino acid sequence analysis revealed identical sequences for both EoCP-1 and EoCP-2, which are also identical to that of RANTES, a cytokine that structurally belongs to the interleukin 8 superfamily of leukocyte selective attractants, and that is known to be a "memory-type" T lymphocyte-selective attractant. In the major Eo chemotaxin, EoCP-1, the residues 4 and 5, which in EoCP-2 were found to be serine residues, could not be identified. Electrospray mass spectrometry (ESP-MS) of EoCPs revealed for EoCP-2 a molecular mass of 7,862.8 +/- 1.1 daltons, which is 15.8 mass units higher than the calculated value of RANTES, indicating that EoCP-2 is identical to the full-length cytokine, and oxygenation, probably at methionine residue number 64, has taken place. Upon ESP-MS, EoCP-1 showed an average molecular mass of 8,355 +/- 10 daltons, suggesting O-glycosylation at these serine residues. Both natural forms of RANTES showed strong Eo-chemotactic activity (ED50 = 2 nM) with optimal chemotactic migration at concentrations near 10 nM, however, there were no significant migratory responses with human neutrophils. Chemotactic activity of RANTES for human Eos could be confirmed using recombinant material, which has been found to be as active as the natural forms. Since RANTES gene expression has been detected in activated T lymphocytes, and recombinant RANTES was shown to be a "memory" T lymphocyte-selective attractant, it is now tempting to speculate about an important role of RANTES in clinical situations such as allergene-induced late-phase skin reactions in atopic subjects or asthma, where in affected tissues both memory T cells and Eos are characteristic.