Increased serum interleukin-15 levels in bullous skin diseases: correlation with disease intensity.
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Adult↗
Biomedical subjects
C Bonifati
Publications and source records attributed to C Bonifati.
Increased serum IL-6, TNF-alpha and IL-10 levels in patients with bullous pemphigoid: relationships with disease activity.
AIM: The present report analyzes the serum levels of three cytokines, interleukin-6 (IL-6), tumor necrosis factor-alpha (TNF-alpha) and interleukin-10 (IL-10) in 15 patients with bullous pemphigoid (BP) (compared with 20 healthy controls) to evaluate a possible involvement of these biological modulators in the clinical expression of this disease. BACKGROUND: BP is a rare bullous disease of autoimmune origin with evidence of inflammatory processes that cause skin lesions with local increase of various pro-inflammatory mediators. METHODS: Determination of cytokine concentrations were obtained employing commercially available ELISA kits. RESULTS: The sera of BP patients showed increased levels of these three cytokines (P < 0.01). When the number of skin lesions (blisters and/or erosion) of each patient, employed as a marker of disease activity, was correlated with the serum levels of IL-6 and TNF-alpha, significant correlations were found (IL-6: P < 0.01 and TNF-alpha: P < 0.01, respectively), suggesting a possible role of these mediators in the development of BP blisters. The serum levels of IL-6 also correlated (P = 0.01 with those of serum C reactive protein (CRP), an acute-phase protein induced by IL-6 in hepatocytes. In addition, serum TNF-alpha and sE-selectin (an adhesion molecule previously reported to be increased by this cytokine) levels were also correlated (P < 0.05). CONCLUSIONS: On the basis of these data, it may be indicated that at least IL-6 and TNF-alpha are associated with the clinical expression of BP and that the endothelial activation (possibly induced by the TNF-alpha activity), seems to be an important phase of this dermatosis.
Adult↗
Immunomagnetic isolation of human developing motor neurons.
Human motor neuron (MN) isolation provides a critical tool to study neurophysiological properties and the effects of molecules of clinical relevance on isolated neurons. We developed an immunomagnetic separation technique based on specific MN antigen recognition for nerve growth factor receptor (p75-NGFR). We cultured an average of 250,000 cells from the anterior horns of a single cord (four specimens at postconception Weeks 6.0, 7.2, 8.0, and 8.3). At day 7 in vitro (DIV), choline acetyltransferase (ChAT) and/or p75-NGFR-expressing cells (MNs) represented 72 +/- 2% of the total growing cells. MNs survived for at least 4 weeks in biochemically defined medium. The immunomagnetic separation method has been demonstrated to be effective, reproducible, and quantitative for separation of MNs.
Cells, Cultured↗
Cytokine pattern in blister fluid and serum of patients with bullous pemphigoid: relationships with disease intensity.
Few and contrasting data are available in the literature concerning the levels of various cytokines in blister fluid (BF) and in the serum of patients affected with bullous pemphigoid (BP). Using commercially available ELISA kits, this study reports the levels of 11 cytokines detected both in BF and sera of 15 BP patients and compares them with those of 15 control subjects' sera. Generally, no significant differences were observed in BP and control sera. In contrast, interleukin (IL) 1 beta, IL-2, IL-4, IL-5, IL-6, IL-8, tumour necrosis factor-alpha (TNF-alpha) and interferon-gamma (IFN-gamma) showed increased BF levels as compared with BP sera. Two cytokines, IL-11 and IL-12 did not show significant differences between BP BF and sera, while an opposite behaviour was observed for transforming growth factor beta 1 (TGF-beta 1), whose serum levels were higher than the concentrations in BF. Using the number of lesions of the patients as a possible disease intensity marker, significant correlations were found with the BF levels of IL-1 beta, IL-8, TNF-alpha and, most closely, IL-5. These data may have pathogenetic relevance and suggest the possibility that these biological modulators may be used as a quantitative marker of disease intensity.
Aged↗
Bullous pemphigoid blisters of the same duration have similar cytokine concentrations which decrease in older blisters.
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Aged↗
Endothelin-1 levels are increased in sera and lesional skin extracts of psoriatic patients and correlate with disease severity.
Endothelins (ETs), in addition to their systematical activities, exert important functions at the skin level, such as increase of keratinocyte proliferation, neo-angiogenesis and leukocyte chemotaxis, which are among the main characteristics of psoriasis. To assess a possible ET-1 involvement in plaque-type psoriasis, ET-1 determinations were carried out in 15 sera and 8 lesional and non-lesional biopsy skin extracts from psoriatic patients and in 15 sera and 5 biopsy skin extracts from healthy volunteers, sex- and age-matched, using commercially available ELISA kits. A statistical analysis of the results showed that ET-1 levels were increased in sera of psoriatic patients, as compared to normal subjects (p = 0.04). In addition, there was a significant correlation between both serum (r = 0.60, p = 0.02) and lesional skin (r = 0.80, p = 0.03) ET-1 values versus the Psoriasis Area and Severity Index scores. Significant increases of the lesional versus the non-lesional (p = 0.01) and versus the normal (p = 0.04) ET-1 skin extract values were observed, together with a significant correlation between lesional and non-lesional ET-1 skin levels (r = 0.79, p = 0.03). These findings were also confirmed at the mRNA level, using RT-PCR analysis, where increased ET-1 mRNA levels, densitometrically measured, were found in the lesional samples versus non-lesional and normal skin. Since interleukin-8 is involved in psoriasis and shares some biological properties with ET-1, we further evaluated the levels of this cytokine in skin extracts. The behaviour of interleukin-8 paralleled that of ET-1, and a significant correlation between these two molecules was observed in the lesional skin (r = 0.76, p = 0.05). Taken together, these data stress that, as previously described for interleukin-8, ET-1 may be involved in inflammatory processes associated with psoriasis.
Adult↗
Decreased interleukin-7 and transforming growth factor-beta1 levels in blister fluids as compared to the respective serum levels in patients with bullous pemphigoid. Opposite behavior of TNF-alpha, interleukin-4 and interleukin-10.
This study analyzes both the blister fluid (BF) and serum levels of IL-7 and TGF-beta1 in samples from 18 patients affected with bullous pemphigoid (BP). These cytokines clearly present lower concentrations (P<0.001) in BFs than in the sera (1/20 and 1/2, respectively). In contrast, TNF-alpha, IL-10 and IL-4 present increased amounts in BFs that were 12, 12 and 17-fold, respectively. Eighteen sera (and 10 suction BF) from normal individuals were also employed as control. Normal sera presented significantly lower serum IL-7 concentrations than BP, while no significant TGF-beta1 variations were observed between normal and pathologic serum samples. In addition, the serum levels detected in BP patients were significantly correlated with disease intensity (r=0.64, P=0.003, evaluated as the number of blisters/erosions for each patient) as well as with the peripheral B-lymphocyte counts (r=0.80, P<0.001) and antibodies directed against the basement membrane zone (r=0.65, P<0.005). Although a clear explanation of this phenomenon is lacking, the data presented in this report agree with a strong decrease of IL-7 production at the local level (keratinocyte is known to produce IL-7 and the latter is known to be down-regulated by IL-10, and in other models also by TGF-beta1 and IL-4, whose levels are elevated in BP BFs) as opposed to an increased peripheral release of the same modulator. The IL-7 reduction may have a biological relevance in controlling a chronic, progressive disease.
Adult↗
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.
Aged↗
Increased interleukin-7 concentrations in lesional skin and in the sera of patients with plaque-type psoriasis.
Several cytokines have been shown to be increased in psoriasis, mainly at the local and sometimes at the systemic level. At present, no data concerning the relationships between psoriasis and interleukin-7 (IL-7) are available. This biological modifier regulates immune response by means of its pleomorphic activities, including the ability to stimulate different monocyte functions, such as killing of intracellular pathogens, induction of cytokines, and enhancement of some membrane molecule expression. Study groups consisted of nine psoriatic and nine normal subjects. Using a commercially available immune-enzyme method, IL-7 concentrations were determined in various samples: biopsy and scale extracts, peripheral blood mononuclear cells (PBMCs) supernatants, and sera. The results show that IL-7 levels are significantly increased both in biopsy and in scale extracts obtained from lesional skin compared to those obtained from nonlesional and normal skin (P at least < 0.01). In addition, the serum values were higher in psoriatic patients than in the controls (P = 0.003). In contrast, no significant differences were observed in the supernatants of unstimulated PBMCs maintained in culture for 48 hr. These data suggest that IL-7 is involved in some way in the pathomechanisms of psoriasis and that the keratinocyte may be a candidate for psoriatic IL-7 overproduction.
Adult↗
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.
Adult↗
Effect of data normalization for age on the correlations between corneometric values and serum molecule levels in plaque-type psoriatic patients.
Corneometry has been considered useful both to evaluate disease severity and to monitor psoriatic patients during treatment. However, a limitation of this technique is that the patient's age influences the corneometric determinations, thus reducing their clinical usefulness. The aim of this study was, therefore, to establish whether age normalization of the corneometric results may provide more reliable data for clinical use. Corneometric levels were determined in 10 plaque-type psoriatic patients, under standard conditions. Eight serum variables, including transforming growth factor-beta 1 and seven soluble membrane molecules, were assayed with commercially available immune-enzyme methods in the same patients, whose age and PASI scores were also recorded. The age normalization procedure improved all the correlation coefficients calculated on the lesional or non-lesional corneometric values versus the PASI scores as well as versus the other serum variables. This approach may render corneometric determinations more useful to evaluate disease status or treatment effect in patient groups with plaque-type psoriasis.
Adult↗
Abnormal corneometric values of non-lesional plaque-type psoriatic skin.
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Adult↗
The serum levels of sE-selectin are increased in patients with bullous pemphigoid or pemphigus vulgaris. Correlation with the number of skin lesions and recovery after corsticosteroid therapy.
Soluble E (sE)-selectin represents the soluble isoform of cellular E-selectin, an adhesion molecule synthesized only by endothelial cells. As a consequence, it may be considered a marker of endothelial activity. The aim of this study was therefore to evaluate the serum levels of sE-selectin in nine patients affected with pemphigus vulgaris (PV) and in 15 patients with bullous pemphigold (BP). Higher amounts of sE-selectin, median 40.3 ng/mL, range 30-109.6 were found in the patients when compared with 20 healthy individuals, median 28.5 ng/mL, range 6.4-48; P < 0.01, matched for sex and age. These levels were also significantly correlated with the number of detectable lesions (r = 0.63, P < 0.001) when the patient data were considered at the time of the first observation. Thirteen subjects were followed over time for a maximum of 3 months (from three to seven observations). During therapy, the number of lesions and the serum sE-selectin values decreased concomitantly. Differently from sE-selectin, the serum soluble intercellular adhesion molecule-1 (sICAM-1) values were not significantly different in the patients from the controls and showed no correlation with the serum sE-selectin concentrations or with the number of lesions. The data presented point to the possible use of sE-selectin determinations as a non-specific follow-up marker, suitable to gauge disease intensity over time and emphasize that endothelial activation is present in BP as well as in PV.
Administration, Topical↗
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.
Adult↗
CD4 Lymphocyte enumeration: comparison between flow cytometry and enzyme immunoassay.
Assessment of the CD4 lymphocyte number, currently performed by flow cytometry, is one of the main laboratory tests for establishing progression to acquired immunodeficiency syndrome (AIDS). An enzyme immunoassay has recently been commercialized which can be very useful for counting CD4 cells in laboratories where flow cytometers are not available. In the present study, a comparative evaluation of CD4 positive lymphocytes with flow cytometry and the enzyme assay was made in healthy subjects (N = 30, R = 0.88, P < 0.0001), human immunodeficiency virus (HIV)-infected individuals (N = 80, R = 0.91, P < 0.0001), and patients with autoimmune diseases (N = 28, R = 0.82, P < 0.001) or psoriasis (N = 18, R = 0.76, P = 0.01). A correlation between the two methodologies was not found in psoriatic patients under treatment with cyclosporin A (N = 7, R = 0.05, not significant). Some differences could be found at low CD4 lymphocyte levels since the influence of CD4 antigen eluted from monocytes or soluble CD4 in the whole blood sample could cause overestimation of CD4 cell numbers by the enzyme assay.
Acquired Immunodeficiency Syndrome↗
Correlation of lesional skin corneometry values with serum E-selectin levels and disease severity in patients affected by plaque-type psoriasis: recovery after effective therapy.
Ten subjects with plaque-type psoriasis (5 females, 5 males, median age 47, range 20-71 years, median psoriasis area and severity index [PASI] score = 15.5, range 8.1-23.0) were observed before (week 0) and at the second and sixth week after starting treatment (PASI = 10.5, range 7.8-14.6; PASI = 8.5, range 1.6-11.6, respectively). At each of these times, the patients were evaluated for both lesional and unlesional skin corneometry and serum E-selectin values, previously shown to be increased in psoriatic subjects. At time 0, both the corneometry and the E-selectin values were significantly correlated with the PASI, infiltration and desquamation scores. As expected, the corneometry was statistically higher in the unlesional than in the lesional areas (p < 0.001). After therapy, the lesion improvement was related both to the PASI scores and E-selectin level decreases (from median levels of 15.5 to 8.5 and from 18 to 13.2 ng/ml, respectively, p < 0.05) as well as to the corneometric level increases (from a median value of 34.5 to 42, p < 0.05). Considering the data obtained at all of these times, significant correlations were found between the PASI scores, lesional skin corneometry and serum E-selectin levels. In conclusion, lesional corneometry seems to represent an objective alternative method for reliably monitoring psoriatic patients.
Adult↗
Soluble E-selectin and soluble tumour necrosis factor receptor (60 kD) serum levels in patients with psoriasis.
BACKGROUND: Increased tumour necrosis factor alpha has been found in psoriatic skin. This cytokine activates endothelial cells and induces the membrane E-selectin molecule (E-selectin or endothelial leucocyte adhesion molecule 1); the same cytokine is able to induce its own receptors. Since the soluble forms of E-selectin and tumour necrosis factor receptor (TNF-R, 60 kD) may be reliably measured in body fluids, these determinations have been performed in the sera of psoriatic patients. OBJECTIVE: To evaluate endothelial activation in psoriatic patients, sE-selectin has been determined in patient sera and compared with those of a control group. sTNF-R (60 kD) was also measured in the same samples. METHODS: Two commercially available enzyme immunoassay methods have been used to determine sE-selectin and sTNF-R (60 kD) in the sera of 19 patients with plaque-type psoriasis; 22 healthy subjects were used as controls. CONCLUSIONS: Significantly increased amounts of sE-selectin serum levels were found in psoriatic patients as compared to healthy controls. Moreover, a direct correlation between sE-selectin and PASI scores was observed. On the contrary, sTNF-R (60 kD) serum levels presented no increases. These data suggest that sE-selectin serum levels are a reliable marker of disease activity in psoriatic patients.
Adolescent↗