No abstract

The toxic effects of exogenous hydrogen sulfide on peripheral blood lymphocytes have been investigated in detail. Hydrogen sulfide is now considered as a gasotransmitter with specific functional roles in different cell types, like neurons and vascular smooth muscle. Here we show that exogenous hydrogen sulfide induces a caspase-independent cell death of peripheral blood lymphocytes that depends on their intracellular glutathion levels, with a physiologically relevant subset specificity for CD8 þ T cells and NK cells. Although lymphocyte activation does not modify their sensitivity to HS À , after 24 h exposure to hydrogen sulfide surviving lymphocyte subsets show a dramatically decreased proliferation in response to mitogens and a reduced IL-2 production. Overall, our data demonstrate that HS À reduces the cellular cytotoxic response of peripheral blood lymphocytes as well as their production of IL-2, therefore de-activating the major players of local inflammatory responses, adding new basic knowledge to the clinically well known anti-inflammatory effects of sulfur compounds.

Background: Subacute cutaneous lupus erythematosus (SCLE) is a distinct subset of cutaneous lupus erythematosus clinically characterized by psoriasiform and/or annular lesions and by a mild or absent systemic involvement. Objective: The Italian Group of Immunodermatology of the Italian Society of Dermatology and Venereology reviewed the cases of SCLE seen in 10 years (1987–1996). Patients: Forty-six women and 12 men have been retrospectively studied, 42% had annular lesions, 39% psoriasiform ones and 16% both. Results: Lesions were mainly localized on the neck and face and relapsed in spring and autumn. Seventeen patients had 4 or more American College of Rheumatology criteria and could be classified as having systemic lupus erythematosus. The most frequent histopathological alterations were epidermal atrophy, hydropic degeneration of the basal layer and perivascular lymphocytic infiltrate. Deposits of immunoglobulins and C3 at the dermo-epidermal junction on the clinically involved skin were present in 86% of the patients. Dust-like particles in the epidermis were only found in 3% of cases. Anti-Ro/SSA antibodies were found in 71% of the cases and anti-dsDNA only in 5% of cases. Conclusions: SCLE is a particular subset of cutaneous lupus erythematosus with peculiar clinical and immunopathological features.

Background: The optimal therapeutic regimen of bath-PUVA therapy of psoriasis is still under debate. Objective: We investigated the safety and efficacy of an aggressive and individualized bath-PUVA regimen. Methods: Two closely matched groups of 22 psoriatic patients were treated either with 30-min baths in 0.0003% 8-methoxypsoralen (8-MOP) aqueous solution or oral administration of the drug. According to the standard European regimen, treatments were delivered 4 times a week starting with the minimal phototoxic dose. Results: Complete clearing or marked improvement was observed in all the patients. However, with bath-PUVA, the same therapeutic effect required smaller cumulative UVA doses (39.3 ± 15.8 vs. 123.8 ± 39.9 J/cm²) and lower numbers of exposures (15.2 ± 4.4 vs. 20.6 ± 4.2). Both differences were significant at the 0.01 level (Student’s t test). Gastrointestinal side effects were of course restricted to oral 8-MOP. The incidences of burns and pruritus were similar. Conclusion: Using an aggressive and individualized schedule, bath-PUVA therapy showed a greater efficacy than oral PUVA therapy while being just as safe.

The effects of exogenous hydrogen sulfide (H 2 S) on normal skin-derived immortalized human keratinocytes have been investigated in detail. We show in vitro that exogenous hydrogen sulfide reduces clonal growth, cell proliferation and cell adhesion of human keratinocytes. H 2 S, in fact, decreases the frequency of the putative keratinocyte stem cell subpopulation in culture, consequently affecting clonal growth, and impairs cell proliferation and adhesion of mature cells. As a mechanistic explanation of these effects, we show at the molecular level that (i) H 2 S reduces the Raf/MAPK kinase/ERK signaling pathway; (ii) the reduced adhesion of sulfur-treated cells is associated to the downregulation of the expression of b4, a2 and a6 integrins that are necessary to promote cell adhesion as well as anti-apoptotic and proliferative signaling in normal keratinocytes. One specific interest of the effects of sulfurs on keratinocytes derives from the potential applications of the results, as sulfur is able to penetrate the skin and a sulfur-rich balneotherapy has been known for long to be effective in the treatment of psoriasis. Thus, the relevance of our findings to the pathophysiology of psoriasis was tested in vivo by treating psoriatic lesions with sulfurs at a concentration comparable to that most commonly found in sulfurous natural springs. In agreement with the in vitro observations, the immunohistochemical analysis of patient biopsies showed a specific downregulation of ERK activation levels, the key molecular event in the sulfur-induced effects on keratinocytes.