Surfactins modulate the lateral organization of fluorescent membrane polar lipids: a new tool to study drug:membrane interaction and assessment of the role of cholesterol and drug acyl chain length.

The lipopeptide surfactin exhibits promising antimicrobial activities which are hampered by haemolytic toxicity. Rational design of new surfactin molecules, based on a better understanding of membrane:surfactin interaction, is thus crucial. We here performed bioimaging of lateral membrane lipid heterogeneity in adherent living human red blood cells (RBCs), as a new relevant bioassay, and explored its potential to better understand membrane:surfactin interactions. RBCs show (sub)micrometric membrane domains upon insertion of BODIPY analogs of glucosylceramide (GlcCer), sphingomyelin (SM) and phosphatidylcholine (PC). These domains exhibit increasing sensitivity to cholesterol depletion by methyl-ß-cyclodextrin. At concentrations well below critical micellar concentration, natural cyclic surfactin increased the formation of PC and SM, but not GlcCer, domains, suggesting preferential interaction with lipid assemblies with the highest vulnerability to methyl-ß-cyclodextrin. Surfactin not only reversed disappearance of SM domains upon cholesterol depletion but further increased PC domain abundance over control RBCs, indicating that surfactin can substitute cholesterol to promote micrometric domains. Surfactin sensitized excimer formation from PC and SM domains, suggesting increased lipid recruitment and/or diffusion within domains. Comparison of surfactin congeners differing by geometry, charge and acyl chain length indicated a strong dependence on acyl chain length. Thus, bioimaging of micrometric lipid domains is a visual powerful tool, revealing that intrinsic lipid domain organization, cholesterol abundance and drug acyl chain length are key parameters for membrane:surfactin interaction. Implications for surfactin preferential location in domains or at their boundaries are discussed and may be useful for rational design of better surfactin molecules.

The combined administration of LNC-encapsulated retinoic acid and calcitriol stimulates oligodendrocyte progenitor cell differentiation in vitro and in vivo after intranasal administration.

Intranasal administration is an efficient strategy for bypassing the BBB, favoring drug accumulation in the brain, and improving its efficiency. Lipid nanocapsules (LNC) are suitable nanocarriers for the delivery of lipophilic drugs via this route and can be used to encapsulate lipophilic molecules such as retinoic acid (RA) and calcitriol (Cal). As the hallmarks of multiple sclerosis (MS) are neuroinflammation and oligodendrocyte loss, our hypothesis was that by combining two molecules known for their pro-differentiating properties, encapsulated in LNC, and delivered by intranasal administration, we would stimulate oligodendrocyte progenitor cells (OPC) differentiation into oligodendrocytes and provide a new pro-remyelinating therapy. LNC loaded with RA (LNC-RA) and Cal (LNC-Cal) were stable for at least 8 weeks. The combination of RA and Cal was more efficient than the molecules alone, encapsulated or not, on OPC differentiation in vitro and decreased microglia cell activation in a dose-dependent manner. After the combined intranasal administration of LNC-RA and LNC-Cal in a mouse cuprizone model of demyelination, increased MBP staining was observed in the corpus callosum. In conclusion, intranasal delivery of lipophilic drugs encapsulated in LNC is a promising strategy for myelinating therapies.

Volcanic monitoring of the 2021 La Palma eruption using long-period magnetotelluric data.

Between September and December 2021, the first subaerial volcanic eruption in the Canary Islands in 50 years took place on the island of La Palma. Since November 2021, we have been conducting a long-period magnetotelluric (MT) monitoring experiment at a site located 2.4 km east of the volcanic cone. Having continuously recorded data since then, the obtained dataset shows significant changes in resistivity over the fourteen months following the eruption: more than ± 20% in apparent resistivity and ± 2 degrees in phase. These temporal variations in electrical resistivity, recorded continuously using long-period MT during both the syn- and post-eruptive stages, have not been reported to date, making this dataset unique. Four estimated impedances have been selected as representatives of the major temporal changes observed and inverted to generate new 3-D resistivity models. The results provide novel key information on the spatiotemporal evolution of the subsoil's electrical resistivity, enabling the characterization of a set of structures acting as preferred magmatic fluid pathways. Therefore, our study highlights the strong potential of MT as a volcanic monitoring tool and provides new insights about the evolution of the fluid pathways during the post-eruptive stage. These findings enhance our understanding of the magmatic system and may contribute to volcanic hazard mitigation in the future.

Three unrelated sphingomyelin analogs spontaneously cluster into plasma membrane micrometric domains.

Micrometric lipid compartmentation at the plasma membrane is disputed. Using live confocal imaging, we found that three unrelated fluorescent sphingomyelin (SM) analogs spontaneously clustered at the outer leaflet into micrometric domains, contrasting with homogeneous labelling by DiIC18 and TMA-DPH. In erythrocytes, these domains were round, randomly distributed, and reversibly coalesced under hypotonicity. BODIPY-SM and -glucosylceramide showed distinct temperature-dependence, in the same ranking as Tm for corresponding natural lipids, indicating phase behaviour. Scanning electron microscopy excluded micrometric surface structural features. In CHO cells, similar surface micrometric patches were produced by either direct BODIPY-SM insertion or intracellular processing from BODIPY-ceramide, ruling out aggregation artefacts. BODIPY-SM surface micrometric patches were refractory to endocytosis block or actin depolymerization and clustered upon cholesterol deprivation, indicating self-clustering at the plasma membrane. BODIPY-SM excimers further suggested clustering in ordered domains. Segregation of BODIPY-SM and -lactosylceramide micrometric domains showed coexistence of distinct phases. Consistent with micrometric domain boundaries, fluorescence recovery after photobleaching (FRAP) revealed restriction of BODIPY-SM lateral diffusion over long-range, but not short-range, contrasting with comparable high mobile fraction of BODIPY-lactosylceramide in both ranges. Controlled perturbations of endogenous SM pool similarly affected BODIPY-SM domain size by confocal imaging and its mobile fraction by FRAP. The latter evidence supports the hypothesis that, as shown for BODIPY-SM, endogenous SM spontaneously clusters at the plasmalemma outer leaflet of living cells into ordered micrometric domains, defined in shape by liquid-phase coexistence and in size by membrane tension and cholesterol. This proposal remains speculative and calls for further investigations.

Clues on the origin of post-2000 earthquakes at Campi Flegrei caldera (Italy).

The inter-arrival times of the post 2000 seismicity at Campi Flegrei caldera are statistically distributed into different populations. The low inter-arrival times population represents swarm events, while the high inter-arrival times population marks background seismicity. Here, we show that the background seismicity is increasing at the same rate of (1) the ground uplift and (2) the concentration of the fumarolic gas specie more sensitive to temperature. The seismic temporal increase is strongly correlated with the results of recent simulations, modelling injection of magmatic fluids in the Campi Flegrei hydrothermal system. These concurrent variations point to a unique process of temperature-pressure increase of the hydrothermal system controlling geophysical and geochemical signals at the caldera. Our results thus show that the occurrence of background seismicity is an excellent parameter to monitor the current unrest of the caldera.

Cytokines and bullous pemphigoid.

This report reviews the data presented in the literature concerning the presence and levels of different cytokines in sera, lesional tissue or blister fluids of patients with bullous pemphigoid. The list of cytokines analysed includes 21 molecules: interleukins (IL)-1 => 8, IL-10 => 13, IL-15, granulocyte-monocyte-colony stimulating factor (GM-CSF), interferon-gamma (IFN-gamma), oncostatin-M (OSM), regulated upon activation normal T cell expressed and presumably secreted (RANTES), transforming growth factor-beta 1 (TGF-beta 1), tumor necrosis factor-alpha (TNF-alpha) and vascular endothelial growth factor (VEGF). Basic information regarding the functions of these cytokines and their possible involvement in the pathogenetic steps of the disease, such as autoantigen expression, autoantibody induction, complement activation, local cell recruitment and stimulation, resident cell activation, release of various effector molecules and tissue damage are also reported. A specific function for each cytokine in bullous pemphigoid induction cannot be still defined, however, the literature attributes a major role to IL-1, IL-4, IL-5, IL-6, IL-8 and IFN-gamma. On the basis of significant (direct or inverse) correlations found between disease intensity and the blister fluid/serum levels, the following cytokines IL-7, IL-15, RANTES, VEGF and TNF-alpha, besides those previously mentioned, may also be involved in this disease.

Cytokines in the sera of patients with pemphigus vulgaris: interleukin-6 and tumour necrosis factor-alpha levels are significantly increased as compared to healthy subjects and correlate with disease activity.

Cytokine serum levels, when detectable, are currently measured in many disease states, both to evaluate a possible pathogenetic involvement of such molecules and for clinical purposes. No data are currently available on the cytokine levels in the sera of patients with pemphigus vulgaris (PV), a rare bullous disease of autoimmune origin. This study presents data concerning the levels of 13 different cytokines assayed in the sera of 25 patients affected with PV as compared with 20 healthy subjects using high sensitivity ELISA kits. Of the 13 molecules analyzed, no differences in the levels of most cytokines were observed between pemphigus and control sera, with the exception of tumor necrosis factor-alpha (TNF-alpha) and interleukin-6 (IL-6). Serum TNF-alpha and IL-6 levels were found to be significantly higher in PV patients than in normal controls (p < 0.001). Furthermore, the levels of the two cytokines decreased after one month of corticosteroid therapy. A significant correlation was found between the serum levels of both TNF-alpha and IL-6 and the number of lesions for each patient (p < 0.001). The data presented support an involvement of at least IL-6 and TNF-alpha in the biological modifications associated with PV manifestations.

Recognition and treatment of psoriasis. Special considerations in elderly patients.

Psoriasis is a chronic dermatological disorder that affects 1 to 2% of the general population. Although its aetiology is still unknown, the importance of genetic factors has been confirmed by many studies, mainly in young individuals. With respect to clinical features, plaque-type psoriasis (localised or generalised) is the most common form. At present, there is no cure for psoriasis and the available treatments can only temporarily clear the skin manifestations. The choice of treatment regimen for psoriasis is based on the severity of the disease, the patient's gender, age, treatment history and level of compliance, and the physician's personal experience. All therapies for psoriasis have different and potentially toxic effects. Therefore, a good knowledge of their relative and absolute contraindications, adverse effects and interactions with other drugs is mandatory. The elderly represent a significant proportion of patients with psoriasis because its prevalence increases with age. Physicians, particularly general practitioners, dermatologists and gerontologists, must be aware of the problems that the treatment of psoriasis in the elderly can present. This is especially important because of the increased risk of adverse drug reactions in the elderly.

Spontaneous release of leukemia inhibitory factor and oncostatin-M is increased in supernatants of short-term organ cultures from lesional psoriatic skin.

Several cytokines are increased in psoriatic skin, mainly at the lesional level. Some of these mediators seem to be very important in the pathogenesis of psoriasis since they are thought to stimulate keratinocyte proliferation and/or to drive the inflammatory changes associated with psoriasis. Among the proinflammatory modulators, hematopoietins, which are a family of cytokines sharing a receptor component (the gp130 subunit), have been under intensive investigation in recent years. The hematopoietin family includes interleukin-6 (IL-6), interleukin-11 (IL-11,) leukemia inhibitory factor (LIF), oncostatin-M (OSM), granulocyte colony-stimulating factor (G-CSF), ciliary neurotrophic factor (CNTF) and cardiotrophin. Amounts of two of these molecules, IL-6 and IL-11, have been found to be increased in psoriatic lesions. The present study adds new information concerning the spontaneous release of two hematopoietins, namely LIF and OSM, in 48-h culture supernatants of lesional and nonlesional skin punch biopsies from psoriatic patients and normal subjects. The cytokine determinations were performed using commercially available ELISA kits. The results are expressed as picograms per milligram of tissue, after weight normalization. The levels of LIF released by lesional skin (median 2.4 pg/mg, range 0.05-13.4 pg/mg) were significantly higher than from nonlesional (median 0.4 pg/mg, range under detection limit (UDL)-4.4 pg/mg; P = 0.001) and normal skin (median 0.4 pg/mg, range UDL-0.9 pg/mg; P = 0.005). The OSM levels were also significantly higher in supernatants of lesional skin (median 0.9 pg/mg, range 0.4-5.2 pg/mg) than in supernatants of nonlesional (median 0.2 pg/mg, range UDL-0.8 pg/mg; P = 0.001) and normal skin (median 0.1 pg/mg, range UDL-0.4 pg/mg; P = 0.0001). In addition, interleukin-8 (IL-8), a cytokine involved in the pathomechanisms of psoriasis, showed a similar behaviour when measured in the same samples. Lesional skin showed a median value of 752.5 pg/mg, range 98.8-2063.8 pg/mg, nonlesional skin a median value of 58.3 pg/mg, range UDL-1252.5 pg/mg (P = 0.007) and normal skin a median value of 44.6 pg/mg, range UDL-176.7 pg/mg (P = 0.004). No significant differences were found between nonlesional and normal skin for the three molecules analyzed. Taken together with the fact that at least two other hematopoietins (namely IL-6 and IL-11) are also increased in supernatants of lesional psoriatic skin, these data point to a possible involvement of the hematopoietins in inflammatory processes associated with psoriasis.

Interleukin-11 production is increased in organ cultures of lesional skin of patients with active plaque-type psoriasis as compared with nonlesional and normal skin. Similarity to interleukin-1 beta, interleukin-6 and interleukin-8.

Increased levels of several cytokines, mainly proinflammatory mediators, have been reported in psoriatic lesions. Little information, if any, is available concerning other cytokines, especially those initially studied as marrow differentiation agents. Using the experimental approach of measuring cytokines released by skin organ cultures. IL-11 and three other proinflammatory cytokines (IL-1 beta, IL-6 and IL-8) were determined using commercially available ELISA kits in supernatants of ten biopsies from lesional and nonlesional psoriatic skin areas and in supernatants of biopsies from ten normal volunteers. The results obtained showed that the amounts of IL-11 and the other three modulators were significantly increased in the material from the lesional areas (P < 0.01). The amounts of IL-11, which is known to have functional activity similar to the proinflammatory cytokines and to share a receptor component with IL-6, were also correlated with the disease severity index (R = 0.69, P = 0.04). In addition, a nearly significant correlation was noted between the amounts of IL-11 released by the lesional and the nonlesional skin biopsies (R = 0.66, P = 0.05). More detailed studies are needed to clarify whether IL-11 plays a specific functional role in psoriasis, but this study emphasizes the complexity of the pathogenesis of psoriasis and the cytokine network, including activation of proinflammatory and haemopoietic biological response modifiers, in this disease.

IL-1 alpha, IL-1 beta and psoriasis: conflicting results in the literature. Opposite behaviour of the two cytokines in lesional or non-lesional extracts of whole skin.

A still debated question in the field of the cytokine network in psoriasis is represented by contrasting data reported on the local amount of IL-1 beta amounts, of IL-1 in this dermatosis. In fact previous studies have suggested that there were decreased Il-1 alpha amounts at the lesional level but increased nonfunctional IL-1 beta concentrations as compared to the non-lesional and normal epidermis. However, recent data suggest that IL-1 alpha and, to a lesser extent, IL-1 beta amounts, are both increased and biologically active in the epidermal cell suspension of lesional psoriatic skin as compared to those of normal skin. The data reported in the present paper show that IL-1 alpha levels are decreased in psoriatic lesional extracts of whole skin (mean 2.9 +/- 2 pg/mg) as compared to non-lesional (mean 6.7 +/- 6.2 mg/mg; p = 0.02) or normal skin (mean 13.8 +/- 9.4 pg/mg; p = 0.0002). IL-1 alpha concentrations were also significantly lower in the non-lesional skin than in normal skin (p = 0.02). In contrast, the IL-1 beta levels (mean 1.2 +/- 0.74 pg/mg were higher in the lesional samples than in the non-lesional ones (mean 0.5 +/- 0.4 pg/mg; p = 0.0004) or in normal skin (mean 0.4 +/- 0.2 pg/mg; p = 0.004). No differences in IL-1 beta levels were observed between non-lesional and normal skin (p = 0.3). In addition both IL-1 alpha and IL-1 beta are directly correlated with the disease severity and each other. Our data, extending the Il-1 determination to the whole skin, seem to confirm the previously reported findings at the epidermis level and provide new light on possible interpretation of literature discrepancies.

Relationship between theoretical molecular weight and blister fluid/serum ratio of cytokines and five other molecules evaluated in patients with bullous pemphigoid.

Bullous pemphigoid (BP) blisters contain several molecules, some of which spread into the blisters from the interstitial fluid, while others are produced locally and migrate into the circulation. The calculation of the ratios between blister/serum concentrations may help to distinguish between these two types of molecules. The rules regulating the diffusion of the molecules have been described only in suction blisters, where the theoretical molecular weight (MW) represents one of the principal influencing factors. The aim of the present study was to analyse the relationship between theoretical MWs and the ratios of concentrations of several molecules evaluated both in sera and in blister fluids. Eight cytokines (interleukin-2, interleukin-3, interleukin-4, interleukin-5, interleukin-10, tumor necrosis factor-alpha, oncostatin-M and vascular endothelial growth factor), two acute phase reactants (alpha-1 acid glycoprotein, haptoglobin), albumin, one soluble membrane molecule with adhesion functions (sICAM-1) and the eosinophil cathionic protein (ECP) were measured in samples from 15 patients affected with BP by means of commercially available tests. The data suggest that the MW may influence the rate of diffusion throughout the blister, both in input and output directions, despite the discontinuity observed at the basement membrane level on the BP blister floor.

Bullous pemphigoid and pemphigus vulgaris: correlated behaviour of serum VEGF, sE-selectin and TNF-alpha levels.

BACKGROUND: Recently, we reported that soluble E-selectin (sE-selectin), an isoform of the cell membrane E-selectin, an adhesion molecule synthesized only by endothelial cells, is significantly increased in sera of the patients with bullous pemphigoid (PB) or pemphigus vulgaris. A significant correlation was also found between the serum sE-selectin levels and the number of skin lesions, suggesting the possible use of this molecule to gauge disease intensity before therapy. One of the sE-selectin inducers is tumor nerosis factor-alpha (TNF-alpha), that is also able to enhance vascular endothelial growth factor (VEGF), a strong endothelium activator. OBJECTIVE: On the basis of these observations, the present study was conducted to analyze the serum levels of VEGF, sE-selectin, and TNF-alpha in 8 patients with BP (age: 82, range 54-87, 7 males, 1 female) and in 6 patients affected affected with PV (age: 55, range 44-65; 5 males, 1 female) and to verify possible correlations between these variables and the disease activity, In addition, serum sE-selectin levels were measured over time and compared with the serum anti-epithelium antibodies titers. METHODS: The sE-selectin, VEGF and TNF-alpha levels were measured in the samples by means of commercially available ELISA kit. The same samples were also employed to measure the anti-epithelium antibody titers. RESULTS: Serum VEGF, sE-selectin and TNF-alpha levels were significantly correlated each other (p at least < 0.01). All three variables were also significantly correlated with the number of lesions (p at least < 0.01). Serum VEGF levels were found increased (median = 178 pg/ml, range 37-595) as compared to 28 healthy controls (median = 135 pg/ml, range 18/269, p < 0.05). Also serum TNF-alpha levels were found increased (median = 5.5 pg/ml, range < 0.1-41.0) as compared to 28 healthy controls (median < 0.1 pg/ml, range < 0.1-5.3), p < 0.01). When the patients were observed over time, serum sE-selectin levels highly correlated with the disease intensity in both dermatoses, although with different regression curves. CONCLUSIONS: These data further underline the endothelium involvement in these bullous dermatoses and stress the possibility of employing sE-selectin as a non-specific follow-up marker of both BP and PV.

Serum TNF-alpha levels correlate with disease severity and are reduced by effective therapy in plaque-type psoriasis.

UNLABELLED: TNF-alpha is a pleiotropic cytokine possibly involved in the pathogenesis of psoriasis. OBJECTIVE: to analyze the serum TNF-alpha levels in plaque-type psoriatic patients to evaluate the concentrations, correlation with the severity score and behaviour after therapy. The serum TNF-alpha levels of thirty-seven patients (25 females and 12 males; median age: 52.5 years, range 18-81: median PASI score: 11.4, range 3.5-42) and thirty healthy controls (21 females and 9 males, median age: 48.5 years, range 25-77) were compared after measurements obtained employing commercially available ELISA kits. The median serum TNF-alpha levels of the patients were significantly higher than those of controls (p = 0.004). 30/37 patients were followed over time at 2 and 4 weeks of treatment. Twenty one subjects were also observed after 6 weeks. After effective treatments, both the PASI scores and the cytokine levels were significantly and concomitantly reduced (p < 0.001). Significant correlations were found when the TNF-alpha values were plotted against the PASI scores both at the time of patient enrollment and at all the subsequent times (118 observations). A significant correlation was observed between circulating TNF-alpha and sE-selectin in agreement with a possible functional activity of the cytokine. However, no correlation was found between the cytokine levels and other 4 soluble membrane molecules. Our findings indicate that the molecule studied, although non specific for the disease considered, presents a behaviour paralleling that of the disease severity and therefore might have clinical usefulness, particularly in monitoring the therapeutic effects.

Anti-intercellular substance antibody log titres are correlated with serum concentrations of interleukin-6, interleukin-15 and tumor necrosis factor-alpha in patients with Pemphigus vulgaris relationships with peripheral blood neutrophil counts, disease severity and duration and patients' age.

Pemphigus vulgaris is a rare dermatosis of autoimmune origin, characterized by autoantibodies directed against intercellular substance (AICS) and presenting with intra-epidermal blisters and/or erosions of the skin and mucous membranes. The aim of this paper is to analyze the relationships between serum AICS titers (after log transformation) and: patients' age, disease duration and disease activity; serum cytokine (IL-6, IL-7, IL-15 and TNF-alpha) concentrations and peripheral blood cell counts (namely neutrophils, lymphocytes and natural killer cells). Fifteen consecutive subjects affected with PV were enrolled. Diagnosis was supported by histological examination as well as by direct and indirect immunofluorescence tests. Cytokine determinations were made by means of commercially available ELISA kits. This study shows for the first time that AICS titers have a significant correlation with age of PV patients (R=0.57, p=0.031) and with the disease duration (R=0.73, p=0.002). A correlation between blood neutrophils count and log (AICS) titres was observed (R=0.6, p=0.021). Furthermore, significant correlations were observed between log (AICS) titres and serum IL-15 (R=0.54, p=0.048), serum IL-6 (R=0.53, p=0.05) or serum TNF-alpha concentrations (R=0.53, p=0.05). These data, taken together, show that there are several connections between the log (AICS) titres, some proinflammatory cytokines, peripheral blood neutrophil counts and the numbers of individuals' lesions, suggesting a relationship between AICS production and lesion development.

Diagnostic relevance of polymerase chain reaction technology for T. pallidum in subjects with syphilis in different phases of infection.

Although serology is a valid tool for the clinician to manage syphilis infection, there are still some cases in which evidence of the presence of T. pallidum or its specific components, such as specific DNA segments, may be useful to establish or confirm the diagnosis. In the absence of T. pallidum grown in culture, a nested PCR to amplify a specific segment of the microorganism genome was performed in ulcerative secretions or sera, after DNA extraction, using a commercially available kit. A kit validation was based on the observation of no positivities in patients without ongoing or anamnestic infection (40 patients). On the contrary, patients infected with T. pallidum presented positivities both in ulcerative secretions and in sera with frequencies that depended on the disease phase and type of sample. In fact, even after treatment, ulcerative secretions that were negative in dark-field examination were found to be positive in PCR. In addition, the sera of patients with positive specific IGM (serologically diagnosed syphilis, asymptomatic state) were also positive in PCR. This test could, therefore, be useful to analyze difficult situations, especially when a seropositivity for a previous infection may complicate the serology of a reinfection or when therapies interfere with dark-field microscopic observation.

Compliance with automated peritoneal dialysis.

Compliance in peritoneal dialysis is reported as being a significant problem. In CAPD, the percentage of non-compliant patients varies between 10 and 40%. In APD the phenomenon seems to be more limited, at 15% - 20%. We considered 23 patients who had been on APD for more than 3 months.The dialytic treatment was performed using the Home Choice Pro device to record all the parameters of the dialysis session. The last 30 days of treatment were considered in the assessment of compliance, evaluating differences in daytime and night-time volumes between the prescription and the actual treatment,the length of the night-time session, and the days of treatment. As regards volume and duration, no differences were found compared to the dialytic prescriptions. For the days of treatment, a differencewas onlyfound in 3 patients: 2 self-administered patients missed day of therapy out of 30, and in both cases the missed tretment was ageed with the Centre; non-compliance was only found in 1 patient (4,3%), whose treatment was performed by the family, and who missed 4 days out of 30.

[Monitoring of sE-selectin serum levels in three different dermatoses]. / Monitoraggio dei livelli sierici di sE-selectina in corso di terapia in tre differenti dermatosi.

PURPOSE: To determine the behaviour of serum levels of soluble E-selectin (sE-selectin), the soluble isoform of E-selectin, before/during/after therapy in patients with three. PATIENTS AND METHODS: Using commercially available ELISA kits, serum levels of sE-selectin have been determined in 15 patients with psoriasis, 15 with pemphigus vulgaris and 15 with bullous pemphigoid, and compared with those of 30 healthy subjects. RESULTS: The results showed increased serum levels of sE-selectin in the three groups of patients as compared with those of 30 healthy subjects (p < 0.01). In addition, serum levels were significantly correlated with the disease activity expressed as Psoriasis Area and Severity Index (PASI score) (R = 0.56, p = 0.014) in psoriasis, and as number of the visible lesions (blisters/erosions), in the two bullous dermatoses (R = 0.81, p < 0.01). After therapy, the marker levels were significantly decreased (p < 0.01). CONCLUSIONS: Overall, these data suggest that serum determinations of sE-selectin could represent a clinically useful indicator to monitor therapy.