0000000000082952
AUTHOR
R. E. Schopf
Importance of HLA-DR+ and CD1a+ Epidermal Cells for Cytokine Production in Psoriasis
Psoriasis is an inflammatory skin disease characterised by marked hyperproliferation of keratinocytes in association with vascular expansion, leukocyte infiltration and lymphocyte activation1. Cytokines are thought to play a pivotal role in the pathogenesis. It is speculated that a dysregulation of the cytokine network involving tumor-necrosis-factor-a (TNF-α), interleukin-6 (IL-6) and interleukin-8 (IL-8) might be the basic mechanism of the psoriatic inflammatory response2. TNF-α is the prototype of a proinflammatory peptide exerting immunomodulatory effects. IL-6 is a multifunctional cytokine with a broad range of biological functions in both acute and chronic inflammatory reactions. IL-8…
Crystal-phagocyte interaction in calcinosis interstitialis.
Based on recent findings indicating the stimulation of the respiratory burst in human neutrophils by crystal phagocytosis, ectopic calcified nodules of a patient with calcinosis interstitialis were exposed to autologous granulocytes and monocytes in vitro. The activity of the respiratory burst was determined by luminol-enhanced chemiluminescence. Controls included amorphous monosodium urate, microcrystalline monosodium urate, hydroxyapatite, and zymosan. Microcrystalline monosodium urate elicited a marked stimulation of both granulocytes and monocytes as did hydroxyapatite in granulocytes. Hydroxyapatite caused no stimulation of monocytes, possibly reflecting selective functional modulation…
Seminal plasma-induced suppression of the respiratory burst of polymorphonuclear leukocytes and monocytes.
Summary: Based on recent findings indicating suppression of lymphocytic functions by seminal plasma (SP) we tested the effects of SP from men with normo- and oligozoospermia (n = 7, each) on the generation of luminol-enhanced chemiluminescence (CL) of polymorphonuclear leukocytes (PMN) and monocytes (Mo) stimulated in vitro with zymosan. We found a complete suppression of CL of PMN and Mo by undiluted SP's, 1,000-fold dilutions still induced ≥ 20 percent inhibition. There was no difference between normo- and oligozoospermic men in inhibition of CL both with PMN and Mo. Protein concentrations of SP's were closely the same; all SP were free of the complement components C4 and C3c. After dialy…
Mixed Epidermal Cell Lymphocyte Reaction: HLA-DR+ Cells Exhibit a Greater Immunostimulatory Activity than CD1a+ Cells
Induction and expression of immunity depends upon processing and presentation of antigens to T-cells by bone marrow derived HLA-DR+ antigen presenting cells (APC). In the induction of immunity to cutaneous antigens, the initial stages of this process begin within the skin itself, and both epidermis and dermis contain bone-marrow derived cells that have the capability of processing and presenting antigens. In normal epidermis, HLA-DR expression is believed to be confined to Langerhans cells with Birbeck granules and indeterminate cells without Birbeck granules. In diseased skin, particularly the inflammatory dermatoses, HLA-DR is commonly expressed by keratinocytes and has been related to th…
Effects of ethanol and acetaldehyde on phagocytic functions
Although a number of skin diseases are characterized by the presence of an increased number of phagocytes in their lesions, the effects of alcohol on phagocytic functions are not clearly understood. Therefore, we measured the influence of ethanol and acetaldehyde on the generation of oxygen radicals, chemotaxis and the release of lysosomal enzymes from human phagocytes. We added 0.03%-3% ethanol and 0.005%-0.25% acetaldehyde to cell cultures. We found that both ethanol and acetaldehyde suppressed the generation of oxygen radicals from granulocytes and monocytes; the ID50 was achieved at concentrations of approximately 0.25% for ethanol and 0.03% for acetaldehyde. A significant inhibition of…
Control of the production of oxygen intermediates of human polymorphonuclear leukocytes and monocytes by beta-adrenergic receptors.
The control by beta-adrenergic receptors of the production of oxygen radicals by zymosan-stimulated human polymorphonuclear leukocytes (PMN) and monocytes (M phi) was studied in vitro by means of chemiluminescence. In addition we asked whether PMN and M phi exhibit differential sensitivity to beta-adrenergic stimulation. For beta-adrenergic stimulation we applied fenoterol ranging from 10(-5) to 10(-9) M x 2.7. We found a dose-dependent suppression of the production of oxygen radicals, the ID50 being approximately 10(-6) M both for PMN and M phi. By assessment of lactic dehydrogenase release a cytotoxic effect of the drug could be ruled out. When incubated together with the beta-adrenergic …
Efficacy and tolerability of multiple-dose SDZ IMM 125 in patients with severe psoriasis.
Although cyclosporin is effective in immunosuppression following organ transplantation and in the treatment of psoriasis, its use is limited by its side-effects, notably impaired renal function and hypertension. As SDZ IMM 125, a new derivative of the cyclosporin family, showed considerable immunosuppressive activity in experimental studies, with less effect on renal function, it was considered a potential successor to cyclosporin for both indications. In this multicentre, double-blind, placebo-controlled study, the efficacy and tolerability of 40, 100, 200 and 400 mg SDZ IMM 125 daily were studied in 59 patients with psoriasis. Patients were followed for a period of 5 weeks (4 weeks treatm…
Josamycin Concentration in Human Ejaculate and its Influence on Sperm Motility/Josamycinkonzentrationsbestimmung in menschlichem Ejakulat und deren Einfluß auf die Spermienmotilität
The concentration of josamycin was determined in the split ejaculate of 5 volunteers after oral administration for several days. One aim of this investigation was to examine the penetration of the macrolide antibiotic into the prostate and the seminal vesicles. 2.23 +/- 1.8 micrograms/ml josamycin was found in fraction I of the ejaculate, consisting mostly of prostatic secretion, and 1.56 +/- 1.37 micrograms/ml josamycin in fraction II comprising mainly secretions from the seminal vesicles. The concentrations of josamycin found in both fractions of the ejaculate are clearly comparable with serum levels of the antibiotic. Josamycin thus attains concentrations in the prostate and seminal vesi…
Augmented glucose-6-phosphate dehydrogenase activity and normal penetration and metabolism of dehydroepiandrosterone in mononuclear leukocytes in psoriasis.
The aim of the study was to determine a biochemical basis for the augmented oxidative metabolism found in mononuclear leukocytes (MNL) of patients with active psoriasis. Dehydroepiandrosterone (DHEA) is known to inhibit glucose-6-phosphate dehydrogenase (G-6-PDH). We determined the activity of G-6-PDH as well as the penetration and metabolism of DHEA - diminished plasma concentrations of which have been found in psoriatics previously - in 16 patients with active psoriasis and 16 controls. MNL in patients with psoriasis possessed 52% more (p less than 0.05) G-6-PDH activity, based on cell number, and 34% more (p less than 0.05) activity, based on soluble protein. No difference in DHEA penetr…
A macrophage-suppressing 40-kD protein in a case of pulmonary alveolar proteinosis.
Pulmonary alveolar proteinosis (PAP) is a rare disease of unknown etiology. Macrophage dysfunctions are claimed to be involved in the pathogenesis. We investigated phagocytosis and oxidative metabolism of alveolar macrophages in a case of pulmonary alveolar proteinosis. These cells phagocytize normally and phagocytizable stimulants cause a normal oxidative burst. In response to the membrane signals phorbolmyristate acetate and aggregated immunoglobulin, however, no stimulated turnover of the oxidative metabolism can be observed. A 40-kD protein found in the lavage fluid mediates this macrophage-inhibiting effect. This phenomenon may contribute to the frequent opportunistic infections seen i…
Stimulation of T cells by autologous mononuclear leukocytes and epidermal cells in psoriasis.
Based on reports suggesting aberrant cell-mediated immunity and altered infiltration of immunocompetent cells into the skin in psoriasis, we studied the stimulation of T cells by autologous non-T mononuclear leukocytes (autologous mixed lymphocyte reaction, AMLR) and by epidermal cells isolated from lesional and clinically uninvolved skin in psoriasis (autologous mixed epidermal cell lymphocyte reaction, AMECLR). Age- and sex-matched individuals served as controls. We found that the AMLR in psoriasis (n = 11) was similar to that in healthy controls (n = 16); furthermore, cell proliferation was alike in the presence of either 5% AB-serum or autologous serum. By contrast, while the AMECLR in …
Secukinumab induction and maintenance therapy in moderate-to-severe plaque psoriasis: a randomized, double-blind, placebo-controlled, phase II regimen-finding study
Abstract Background: Interleukin-17A has major proinflammatory activity in psoriatic lesional skin. Objectives: Assess the efficacy and safety of secukinumab, a fully human IgG1κ monoclonal anti-interleukin-17A antibody, in moderate-to-severe plaque psoriasis in a phase II regimen-finding study. Methods: 404 patients were randomised to subcutaneous placebo (67 patients) or one of three secukinumab 150 mg induction regimens: Single (week 0; 66 patients), Early (weeks 0, 1, 2, 4; 133 patients), and Monthly (weeks 0, 4, 8; 138 patients). The primary outcome was ≥75% improvement from baseline Psoriasis Area and Severity Index (PASI) score at week 12. PASI 75 responders from active treatment …
Soluble CD14 monocyte antigen in suction blister fluid and serum of patients with psoriasis.
The purpose of this study was to measure soluble CD14 (sCD14) molecules in the skin and in serum of patients with psoriasis. CD14 is a newly discovered cell surface marker on monocytes that is shed after cell activation. The following procedures were used: suction blisters were raised over the abdominal skin of 9 healthy control individuals and 8 patients with psoriasis. Serum of 17 healthy controls and 17 patients with psoriasis was collected. sCD14 was determined in suction blister fluid and serum by the ELISA technique. The clinical status of psoriasis was rated by the psoriasis area and severity index (PASI score). We found that sCD14 levels in suction blisters of healthy skin (1,050 +/…
Influence of Agents Used for Topical Wound Treatment on Phagocyte Stimulation and Fibroblast Growth
Wound healing has always been a fascinating phenomenon for physicians and surgeons. Wounds usually close by forming new granulation tissue, contracting, and re-epithelializing. Before granulation begins, polymor-phonuclear leukocytes (PMNs) and monocytes/macrophages (MCs) are chemotactically attracted to sites of injury. Upon contact with various stimuli in the wound including bioactive lipids, complement components, certain cytokines, e.g., tumor necrosis factor-α (TNF-α) [1], granulocyte/ monocyte-colony stimulating factor (GM-CSF), interferon-γ (IFN-γ), and interleukin-8, and particles such as microorganisms, phagocytes respond by a respiratory burst consisting of a markedly enhanced upt…
Pyostomatitis vegetans und Morbus Crohn: Eine spezifische Assoziation zweier Krankheiten
HISTORY AND CLINICAL FINDINGS A 27-year-old man was referred to the dermatological out-patient clinic because of inflammatory changes in the oral mucosa of unknown cause. 5 months earlier he had been diagnosed as having Crohn's disease of the terminal ileum. On both sides of the buccal mucosa there were rough erythematous vegetations and disseminated miliary abscesses, which extended to the labial gingiva and the soft palate. Further physical examination was unremarkable. INVESTIGATIONS Several inflammatory parameters were increased: C-reactive protein 100 mg/l, erythrocyte sedimentation rate 55/88 mm, eosinophilic cationic protein 35.8 ng/ml (normal range 2.3-16 ng/ml). White cell count wa…
Soluble intercellular adhesion molecule-1 levels in patients with psoriasis.
A newly developed ELISA was used to detect and quantify the presence of a soluble form of intercellular adhesion molecule-1 (sICAM-1) in the circulation of healthy individuals compared with patients with psoriasis vulgaris. Seventeen psoriatic patients were studied. The extent of skin lesions was rated by the psoriasis area and severity index (PASI). Seventeen age- and sex-matched healthy individuals served as controls. Serum levels were measured by an ELISA technique utilizing an anti-ICAM-1 murine monoclonal antibody bound to the solid phase, and a second, peroxidase-conjugated monoclonal antibody reacting with sICAM-1. Serum levels in controls were 358.8 +/- 87.9 ng/ml sICAM-1, and 480.5…
Chloroquine Stimulates the Mitogen-Driven Lymphocyte Proliferation in Patients with Psoriasis
Chloroquine is known to exacerbate psoriasis. Since immunological stimuli are considered to be important for the pathogenesis of psoriasis, we compared the effects of chloroquine on cell-mediated immunity in 15 healthy control individuals and 15 patients with psoriasis. We employed the spontaneous and phytohemagglutin (PHA)-induced uptake of 3H-thymidine to measure lymphocyte proliferation. Chloroquine was added to the cultures at concentrations ranging from 0.022 to 220 microM. We found that both spontaneous and PHA-driven lymphocyte proliferations were significantly lower in patients with psoriasis (p0.002). The spontaneous blastogenesis in both controls and patients remained stable under…
Granulocyte Activity Is Enhanced by Culture Supernatants of Mononuclear Leukocytes Incubated with Tetrachlorodecaoxide
Granulocytes (polymorphonuclear leukocytes, PMNs) and monocytes/ macrophages are important in wound healing. Within the first few hours PMNs and monocytes begin to infiltrate sites of injury. The major function of PMNs is to kill microbes and phagocytose cellular debris so that healing can proceed [1]. Monocytes/macrophages invading the wound are also active in phagocytosis. In addition they release a number of cytokines including growth factors, interleukin-8 (IL-8), and tumor necrosis factor (TNF-α) needed for new tissue formation and shown to stimulate PMNs [1–3].
Increased respiratory burst activity of monocytes and polymorphonuclear leukocytes in psoriasis.
SUMMARY We studied the respiratory burst activity of peripheral blood monocytes and polymorphonu clear leukocytes (PMN) in eleven patients with psoriasis and eleven healthy controls, using zymosan particles to activate the phagocytes in vitro. The activation of the phagocytes was measured in a luminol-enhanced chemiluminescence (CL) assay. We found a significantly higher respiratory burst activity of both monocytes and PMN in patients with psoriasis compared with the control subjects. The percentages of monocytes in psoriatics did not differ from those of the controls. The higher amount of zymosan-induced CL activity generated in the patient group was unrelated to the age of the individual.…