Platelets secrete an eosinophil-chemotactic cytokine which is a member of the C-C-chemokine family.
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Amino Acid Sequence↗
Biomedical subjects
E Christophers
Publications and source records attributed to E Christophers.
Pro- and anti-inflammatory cytokines in primary systemic vasculitis.
The expression of cytokines that are potentially involved in the pathogenesis of vasculitis was studied in patients with primary systemic vasculitis (PSV). In extension of earlier reports, we detected an overexpression of transforming growth factor beta (TGF beta), interleukin 6 (IL6), and interleukin 8 (IL8), indicating that the whole cytokine cascade is activated to a significant extent in PSV.
Churg-Strauss Syndrome↗
Inhibition of proteinase 3 activity by peptides derived from human epidermis.
Elafin and antileukoprotease are potent peptide-like inhibitors of human leukocyte elastase and have been isolated from human skin and bronchial mucus. Elafin proved to be a potent inhibitor of proteinase 3, whereas other inhibitors of human leukocyte elastase such as antileukoprotease and eglin C proved to be much less effective.
Amino Acid Sequence↗
Antileukoprotease in psoriatic scales.
Antileukoprotease is known to be an antiproteolytic compound of mucous secretions in humans. While searching for peptide-like inhibitors of neutrophil-derived serine proteases in horny layers of human skin, we isolated a potent inhibitor of human leukocyte elastase (EC 3.4.21.37) and cathepsin G (EC 3.4.21.20) from psoriatic scales. This inhibitor showed inhibitory constants for human leukocyte elastase of approximately 0.5-2 x 10(-10) M and for cathepsin G of 2-4 x 10(-9) N. The N-terminal amino acid sequence of the purified peptide matched the sequence of antileukoprotease and both peptides showed the same M(r) on SDS-PAGE. Therefore, antileukoprotease may not only regulate serine protease activities in mucous secretions, but also in skin.
Amino Acid Sequence↗
Time- and stimulus-dependent secretion of NAP-1/IL-8 by human fibroblasts and endothelial cells.
The neutrophil-activating peptide 1/interleukin 8 (NAP-1/IL-8) has in the past been extensively characterized biochemically as well as functionally. Effects of NAP-1/IL-8 on inflammatory cells like neutrophilic granulocytes and lymphocytes, as well as its production by several different cell types, point towards an important role in different inflammatory processes. Recently, monoclonal antibodies have helped to establish immunoassays for detecting the peptide. Using such antibodies, we have performed in vitro studies on the time- and stimulus-dependent production of IL-8 by endothelial cells as well as fibroblasts. Tumor necrosis factor-alpha (TNF-alpha) and interleukin-1 alpha (IL-1 alpha) efficiently induced both focal intracellular expression as well as secretion of the peptide when tested by immunocytochemistry and enzyme-linked immunosorbent assay (ELISA). After stimulation with phorbol myristate acetate (PMA) and lipopolysaccharide (LPS), such effects were seen only in endothelial cells, whereas interferon (IFN)-gamma did not induce any pronounced effect on either of the cells tested. These studies demonstrated in vitro release of IL-8 by different cells upon specific stimulation, thus underlining the significance of the in vivo secretion of this peptide, as noted in recent studies.
Cells, Cultured↗
Highly purified omega-3-polyunsaturated fatty acids for topical treatment of psoriasis. Results of a double-blind, placebo-controlled multicentre study.
We report the results of a multicentre, double-blind, placebo-controlled study of topical therapy with omega-3-polyunsaturated fatty acids (omega-3-PUFA) in 52 patients suffering from moderate plaque-type psoriasis. In each patient, two similar stable psoriatic plaques served as indicator lesions for the study. One indicator lesion was randomly assigned to treatment with topical preparations of highly purified omega-3-PUFA in one of two concentrations (1 or 10%), and the other was treated with placebo. Efficacy assessment was based on changes in local psoriasis severity index, area involved, erythema, desquamation, induration and pruritus. After 8 weeks of treatment, all indicator lesions had improved significantly, compared with baseline. However, no statistically or clinically relevant differences between the omega-3-PUFA-treated and the placebo-treated lesions were found. Therapy was well tolerated and, apart from one patient who developed perilesional eczema, no clinically relevant adverse events occurred. In conclusion, topical omega-3-PUFA were not effective in a randomized, placebo-controlled, double-blind setting. Results of non-blind trials should be (re-)considered with caution.
Administration, Topical↗
Topical tiacrilast, a potent mast cell degranulation inhibitor, does not improve adult atopic eczema.
Tiacrilast is a potent mast cell degranulation inhibitor in vitro and in animal studies. Since mast cells and their mediators are possibly involved in atopic eczema, we have studied a topically applied 3% hydrogel formulation of tiacrilast against vehicle in a multicenter, double-blind, placebo-controlled trial. Drug or vehicle were applied on involved skin for 28 days. Efficacy was assessed weekly using a 4-point scale for erythema, scaling, induration, exudation and pruritus. An overall assessment of the sites for efficacy and site preference was performed at the end of treatment. In the 32 patients evaluable for efficacy, > 33% improvement was noted on 78% of the drug- and 75% of the vehicle-treated sites, with no statistically significant differences for any of the parameters tested. Treatment was generally well tolerated by all patients. These data suggest that mast cells may not play a major role in the maintenance of atopic eczema lesions.
Administration, Cutaneous↗
Azelaic acid has antimycotic properties in vitro.
Azelaic acid is a therapeutic agent with well-known antibacterial properties, but its antimycotic effect has not yet been investigated systematically. In this study we have used an agar dilution technique to test the inhibitory effect of azelaic acid upon common dermatophytes, Scopulariopsis brevicaulis, Candida albicans, Candida glabrata and Pityrosporum ovale. As a result, the growth of dermatophytes and S. brevicaulis was suppressed by 0.56% azelaic acid and that of P. ovale by 1%. By 4% azelaic acid C. glabrata was inhibited completely, but C. albicans still maintained some growth. The antimycotic effect of azelaic acid occurred at pH values between 4.8 and 5.5, whereas its disodium salt had no such effect at pH 6.1. Considering the favorable pharmacological data of azelaic acid, our results give reason to investigate the antimycotic effect of this agent in vivo.
Arthrodermataceae↗
[Comment of the German Dermatologic Society to the therapeutic procedures of a dermatologist].
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Complementary Therapies↗
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.
Amino Acid Sequence↗
Mesna side effects which imitate vasculitis.
Mesna (sodium-2-mercaptoethansulfonate) is used in the prophylaxis of cyclophosphamide (CYC)-induced hemorrhagic cystitis. Four patients being treated with "low dose" CYC and prednisone for vasculitis developed severe side effects to Mesna. Fever, arthralgia, myalgia, tachycardia, electrocardiogram changes consistent with perimyocarditis, erythroderma, bullous skin and mucous membrane lesions, and abdominal complaints with profuse diarrhea were noted approximately 3 weeks after the initiation of therapy for CYC-induced leukopenia and a conservatively reduced prednisone dosage. Positive reexposure tests confirmed the association to Mesna use, and hypersensitivity skin tests demonstrated a delayed hypersensitivity reaction.
Adult↗
Immunohistochemical studies on NAP-1/IL-8 in contact eczema and atopic dermatitis.
The neutrophil activating peptide NAP-1/IL-8 has in the past been shown to be secreted by diverse cell-types involved in inflammatory processes. Furthermore, potent biological effects on both neutrophilic granulocytes and lymphocytes enforce its role in inflammation. Recently, immunohistochemical studies using monoclonal anti-NAP-1/IL-8 antibodies have been performed on dermal inflammatory conditions like psoriasis vulgaris. These have demonstrated epidermal IL-8 immunoreactivity in a pattern inversely related to the degree of inflammatory infiltration. Based on these results, in the present study biopsies from patients with contact eczema as well as atopic dermatitis were examined. The same patterns of immunoreactivity were found with either homogeneous epidermal staining, focally negative staining or overall decreased or even absent staining. As in psoriasis, these patterns were related to the degree of inflammatory infiltration. These results prove NAP-1/IL-8 to be involved not only in psoriasis vulgaris, but more likely to be a marker of different inflammatory processes. Future work will have to examine the kinetics as well as stimuli causing these effect.
Biopsy↗
Cyclosporine in psoriasis: a multicenter dose-finding study in severe plaque psoriasis. The German Multicenter Study.
Interim results of a randomized, controlled, dose-finding study conducted in 24 dermatology centers on 217 patients with severe chronic plaque psoriasis (entry psoriasis area and severity index of at least 15) are presented. Patients were first treated with cyclosporine either 1.25 or 2.5 mg/kg/day (Sandimmune); in case of inadequate response the dosage was increased to a maximum of 5 mg/kg/day. Cyclosporine was given for 12 to 36 weeks. Treatment was classified as "successful" if the psoriasis area and severity index was reduced to 25% or less of the baseline value or below 8. At the end of the treatment period 18% of patients had improved their psoriasis area and severity index "successfully" with the initial dose of 1.25 mg/kg/day. "Successful" improvement with the initial dose of 2.5 mg/kg/day was achieved in 56% of the cases. In the 1.25 mg group, 44 patients had to increase their dose to 2.5 mg/kg/day and 31 patients to 5 mg/kg/day. In 29 patients whose dosages were started at 2.5 mg/kg/day the dosage was subsequently increased to 5 mg/kg/day. Although 1.25 mg/kg/day proved to be effective in some cases, 2.5 mg/kg/day of cyclosporine is the optimal starting dose. Adverse events were observed in 10% of the patients taking 1.25 mg/kg/day, in 20% taking 2.5 mg/kg/day, and in 32% taking 5 mg/kg/day. The most common were gastrointestinal complaints, followed by the common cold and other viral infections. An increase of serum creatinine level above 130 mumols/L occurred in five patients who could continue therapy after reducing the dose.(ABSTRACT TRUNCATED AT 250 WORDS)
Adolescent↗
Hypertriglyceridemia in patients with psoriasis treated with cyclosporine.
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Cyclosporine↗
Neutrophil-activating proteins in psoriasis.
Neutrophil accumulation in the epidermis is a histologic characteristic of psoriasis. We addressed the question: What is the major protein-like chemotactic principle responsible for neutrophil accumulation? Purification of proteinaceous neutrophil chemoattractants from extracts obtained from psoriatic scales by multistep high-performance liquid chromatography (HPLC) yielded three biochemically distinct polypeptides with potent neutrophil chemotactic activity. Aminoterminal amino acid sequence analysis of the quantitatively major neutrophil attractant revealed the sequence ELRXQXIKTYSK, which is identical to that of a 69 residue form of neutrophil-activating peptide-1/interleukin 8 (NAP-1/IL-8). The second major attractant showed the sequence XXVATELRXQXL . . ., which is identical to that of the gene product of the oncogene "gro" as well as "melanoma growth stimulatory activity, MGSA," whereas the third and minor neutrophil chemotaxin has an NH2-terminal sequence identical with NAP-1/IL-8. Estimation of NAP-1/IL-8-related proteins and gro/MGSA by HPLC combined with bioassay revealed a mean of 3.3 +/- 1.7 ng NAP-1/IL-8-related proteins (n = 11) and 3.2 +/- 1.9 ng gro/MGSA (n = 11) per 1 mg psoriatic scales. In normal heel callus (n = 8), these neutrophil attractants were found at concentrations below 0.02 +/- 0.01 ng/mg. The finding of more than 150-times increased amounts of both NAP-1/IL-8 and gro/MGSA in lesional psoriasis material suggest that these mitogenic as well as neutrophil- and lymphocyte-chemotactic compounds may play an important role in the pathogenesis of psoriasis.
Amino Acid Sequence↗
Lesional elastase activity in psoriasis, contact dermatitis, and atopic dermatitis.
Human leukocyte elastase (HLE) is a broad spectrum serine protease derived from neutrophils and macrophages. We developed an assay to determine HLE activity on the skin surface in patients with inflammatory skin diseases. HLE activity was absent in the skin of healthy controls. A massive increase of HLE activity was found in lesional skin of psoriasis (31 times), allergic contact dermatitis (55 times), and atopic dermatitis (35 times), but not in uninvolved skin of diseased patients. Therefore, this assay appears to represent a useful biochemical marker of epidermal inflammation. The presence of proteolytically active HLE in diseased epidermis, which is known to contain specific inhibitors of this enzyme, suggests a pathophysiologic role of this enzymatic activity in psoriasis, contact dermatitis, and atopic dermatitis.
Adult↗
Inhibition of human monocyte functions by anthralin.
Anthralin is a well-established and widely used compound for topical treatment of psoriasis. In recent years attention has been focused on the anti-inflammatory properties of anthralin, with particular reference to psoriasis. In this study the effect of anthralin on human monocyte chemotaxis, superoxide-anion generation, and enzyme degranulation, were investigated. For comparison, the effect of the clinically inactive anthralin derivative danthrone and the solvent (acetone) were also studied. The results show that anthralin potently inhibits stimulated human monocyte superoxide-anion generation and enzyme degranulation, with a half-maximal inhibitory concentration (IC50) of as low as 0.02 micrograms/ml. Chemotactic migration of monocytes, however, was only affected when very high doses of anthralin (10 micrograms/ml) were used for pretreatment of the cells. Danthrone, up to a concentration of 10 micrograms/ml, or acetone alone (0.1%, v/v), did not inhibit the monocyte functions tested. Our results indicate that anthralin at pharmacological concentrations is a potent and selective inhibitor of human monocyte pro-inflammatory activities, by inhibiting respiratory burst activity (e.g. superoxide-anion generation) and enzyme degranulation, without affecting chemotactic migration.
Acetone↗