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Biomedical subjects

K Thestrup-Pedersen

Publications and source records attributed to K Thestrup-Pedersen.

At least 109 records · Page 6Linked to original sources
PubMed1991

1,25(OH)2-D3 is a potent regulator of interleukin-1 induced interleukin-8 expression and production.

Interleukin 8 (IL-8) is a potent leukocyte chemotactic and activating cytokine produced by keratinocytes, fibroblasts, peripheral blood monocytes (PBMC) and endothelial cells. IL-8 is believed to play an important role in the development of inflammation and is thus an obvious target for therapeutical modulation. We studied the possible effect of an endogenous immune modulator 1,25(OH)2-cholecalciferol (1,25(OH)2-D3) on the IL-1-induced IL-8-production by several types of cells. 1,25(OH)2-D3 inhibited the IL-1-alpha induced IL-8 production and mRNA expression in keratinocytes, fibroblasts and PBMC, but not in endothelial cells. Optimal vitamin concentrations varied between 10(-10) and 10(-11) M. These results suggest a potential role of this hormone in the regulation of chemotactic cytokine production.

Calcitriol↗
PubMed1991

Recombinant human interleukin-8 is a potent activator of canine neutrophil aggregation, migration, and leukotriene B4 biosynthesis.

Interleukin-8 (IL-8), formerly known as NAP-1, is formed by a variety of cells upon stimulation with IL-1 or tumor necrosis factor (TNF). The biologic activity of the cytokine involves activation of almost every neutrophil function studied so far in different species. In the present study, we compared the effects of recombinant human IL-8 (rIL-8) and the lipid mediators, leukotriene B4 (LTB4) and platelet-activating factor (PAF), on neutrophil functions in dogs. All three chemotactic factors induced neutrophil aggregation and chemotaxis, with rIL-8 being far more potent than LTB4 and PAF. The migration induced by rIL-8 was significantly greater than that observed towards LTB4 and PAF. In the aggregation assay, rIL-8 was shown for the first time to be a potent stimulant. The aggregation response was more persistent than that obtained with LTB4 and PAF and the potency of rIL-8 was greater. An intradermal dose-response study showed that rIL-8 is an extremely potent inducer of selective neutrophil infiltration in canine skin. The infiltration was more pronounced than following injection of LTB4 or PAF. It was proposed that the superior effect of rIL-8 was caused by a synergistic effect between injected rIL-8 and LTB4, which was shown to be produced in biologically active amounts by canine neutrophils stimulated with rIL-8. From a therapeutic point of view, the simultaneous presence of rIL-8 and LTB4 in inflammatory skin diseases highlights the need to develop drugs that inhibit the production and/or effect of both mediators.

Animals↗
PubMed1991

Quantitative determination of IL-1 alpha-induced IL-8 mRNA levels in cultured human keratinocytes, dermal fibroblasts, endothelial cells, and monocytes.

The presence of the leukocyte chemotactic cytokine interleukin 8 (IL-8) in psoriatic scales and in epidermal tissue overlying allergic patch test reactions suggests a role for this cytokine in certain inflammatory skin diseases. IL-8 can be produced by several cell types present in the skin. Their relative potentials for IL-8 expression has, however, not yet been studied, due to the lack of convenient methods for quantitative comparison of specific mRNA amounts in different cell types. Using a new method for quantification, we compared specific IL-8 mRNA amounts in cultures of keratinocytes, dermal fibroblasts, endothelial cells, and monocytes, stimulated with interleukin 1 alpha (IL-1 alpha). Endothelial cells produced very high, fibroblasts and monocytes intermediate, and keratinocytes low amounts of IL-8 mRNA. We also studied the time course of IL-8 mRNA levels in the four cell types following IL-1 alpha stimulation, and found a clear difference both in onset and stability of the response. We discuss the different strength of the response at different time points in the cell types analyzed in relation to their possible role in regulation of the normal response to stimulation.

Cells, Cultured↗
PubMed1991

Expression and secretion of leukocyte chemotactic cytokines by normal human melanocytes and melanoma cells.

The capacity of human melanocytes and melanoma cells to produce IL-8 and monocyte chemotactic and activating factor (MCAF) was investigated. Melanocytes expressed mRNA for IL-8 and MCAF, when stimulated with either IL-1 alpha or TNF alpha, but not when stimulated with IL-6, IFN gamma, or LPS alone. IL-8 and MCAF could be induced in a dose-dependent fashion with doses as low as 0.1 ng/ml TNF alpha and 0.5 ng/ml IL-1 alpha. IL-8 and MCAF mRNA were rapidly expressed and peaked between 2 and 4 h for IL-8 and between 4 and 8 h for MCAF. This correlated well with the accumulation of IL-8 antigen as measured by a radioimmunoassay. Supernatants from melanocyte cultures stimulated with either IL-1 alpha or TNF alpha and separated on a heparin-Sepharose column became positive for neutrophil and monocyte chemotactic activity in a dose- and time-dependent fashion. When IFN gamma was added to melanocyte cultures stimulated with suboptimal doses of TNF alpha there was a synergistic increase in secreted IL-8 protein and monocyte chemotactic activity. These data provide further evidence for the possible role of melanocytes in the initiation of an inflammatory reaction. Three different malignant melanoma cell lines stimulated with either TNF alpha or IL-1 alpha expressed IL-8 mRNA, but not mRNA for MCAF. The IL-8 mRNA signal corresponded well with the amount of secreted IL-8 protein. These data suggest that IL-8 and MCAF may play a role in growth regulation and spreading of melanomas.

Antigens↗
PubMed1991

Increased tryptase levels in suction-blister fluid from patients with urticaria.

The levels of tryptase in the suction-blister fluid from patients with chronic urticaria, urticaria pigmentosa, cholinergic urticaria, urticarial dermographism, prurigo of unknown origin, eczema, psoriasis, atopic dermatitis, and from healthy controls were studied. The blister fluid from controls contained up to 15 micrograms/l of tryptase, whereas that from patients with active urticaria contained greater than 50 micrograms/l. This study demonstrates that patients with urticaria have mast cells that readily release tryptase in both the lesional and non-lesional areas of skin.

Adult↗
PubMed1991

Skin symptoms among workers in the fish processing industry are caused by high molecular weight compounds.

Scratch tests were performed with fish juice containing high and low molecular weight compounds obtained by ultrafiltration and with degradation compounds known to accumulate in fish stored on ice. 75 volunteers were tested. The peptide pattern in raw fish juice and its high and low molecular weight fractions were analysed by sodium dodecyl sulphate-polyacrylamide gel electrophoresis (SDS-PAGE) and the concentration of protein in the various fractions was determined. Fish products were analysed for bacteria and algae and the concentration of degradation compounds was measured. Mainly high molecular weight compounds (polypeptides) of fish juice were found to be responsible for the skin symptoms.

Adolescent↗
PubMed1991

The relationship between skin surface temperature, transepidermal water loss and electrical capacitance among workers in the fish processing industry: comparison with other occupations. A field study.

A field study among workers in the fish processing industry (n = 143) was performed to obtain information about skin surface temperature, transepidermal water loss (TEWL), and electrical capacitance and their relationships during work. The skin temperature, TEWL and electrical capacitance were measured on the fingers, hands and forearms. A linear positive relation was found between the temperature and TEWL (in all measured areas), a linear negative relation between the temperature and capacitance (fingers and palms), and a linear negative relation between the capacitance and TEWL (fingers). The results on the fingers among workers in the fish processing industry were compared with results among metal workers (n = 52), cleaners (n = 30), gut cleaners (n = 25), nurses (n = 16), office workers with indoor climate syndrome (n = 20) and normal controls (n = 29). A linear positive relation was found between the respective temperature-TEWL values and a linear negative relation between the respective temperature-capacitance values in the various groups. Furthermore the slope of the temperature-TEWL relations was identical in all groups. Therefore, differences in TEWL levels (comparison at the same temperature) between the respective groups and controls and between the various groups might indicate damage to the skin barrier caused by contact with different irritants and chemicals. However, differences in environment-related variables in the various occupations might also affect TEWL levels. This field study demonstrates, from a practical point of view, how the skin temperature affects TEWL in the various occupations and, as a new point, how sensitive capacitance is to changes in skin temperature. Seasonal variation in TEWL and capacitance was demonstrated among workers in the fish processing industry, with a low TEWL and a high capacitance during summer when the workload is lower.

Adolescent↗
PubMed1991

Skin physiological changes in employees in the fish processing industry immediately following work. A field study.

In order to explain the complaints of dry skin after work among employees in the fish processing industry, we followed the skin blood flow (SBF), skin surface temperature, transepidermal water loss (TEWL) and electrical capacitance on the volar aspect of the 3rd finger in 10 fillet workers, where measurements were performed just at the end of a working day and during the next hour. The results were compared with 10 normal controls. During work, a low SBF, temperature and TEWL, and a high capacitance were found. After work, the SBF, temperature and TEWL increased to values above normal within 10-15 min, while the electrical capacitance decreased to subnormal values. A positive relation was demonstrated between skin temperature and TEWL, negative relations between temperature and capacitance, and between capacitance and TEWL. Our results in this field study confirm our clinical findings among workers in the fish processing industry: low occurrence of chapping and eczema during work and the development of dry skin after work.

Adult↗
PubMed1991

Palmar skin is not involved in severe atopic eczema.

Irritant hand eczema is a well-known risk in adults, who have suffered from severe atopic dermatitis during childhood. We therefore studied the involvement of the skin on the hands in 29 consecutive patients admitted for severe atopic dermatitis. Only 5 of the 29 patients had eczema in the palmar skin (p less than 0.01; sign test). There was no correlation with the existence of hyperlinearity, extent of disease, concomitant asthma, total serum IgE or work.

Adolescent↗
PubMed1991

Soluble IL2 receptor serum levels and epidermal cytokines in mycosis fungoides and related disorders.

We examined the immune activation in 20 patients with mycosis fungoides, 6 patients with erythrodermia of unknown origin (Pré-Sézary's syndrome), 5 with lymphomatoid papulosis, 4 with parapsoriasis, 2 with Sézary's syndrome, and 2 with actinic reticuloid, by measuring soluble interleukin-2 receptor levels in serum. In Mycosis fungoides we observed normal levels in 3 patients (less than 500 units/ml), between 500 and 1000 units/ml in 9 patients, and greater than 1000 units/ml in 5 patients. Four of these 5 patients died within one year after this observation, as did 2 patients with Pré-Sézary and Sézary's syndrome, respectively, who had a similarly large increase in sIL2R. Although sIL2R is not a specific parameter for cutaneous T-cell lymphoma, a value above 1000 units/ml is correlated with clinical disease activity and is a serious prognostic parameter. We also studied cytokine activity in epidermal homogenates from 9 patients with Mycosis fungoides and one patient with Sézary's syndrome. We observed interleukin-1-like activity within the normal range for healthy skin. However, we also observed in the same epidermal homogenates a T-lymphocyte chemotactic activity in patients with stage II, but not in stage I. The nature of this activity is not yet fully elucidated, but it may be an important biological factor for the epidermal T-cell accumulation in this disorder.

Aged↗
PubMed1990

[Mycosis fungoides. A review of the clinical picture, treatment and course in 107 patients].

During the period 1972 till the end of 1987, 107 patients with the diagnosis of mycosis fungoides or cutaneous T-cell lymphoma were examined and treated in the Department of Dermatology, Marselisborg Hospital. This disease belongs to the group of non-Hodgkin T-cell lymphomata. The diagnosis is based on the occurrence of red, scaly plaques in the skin associated with itching or tumours in the skin and, simultaneously, of a pleomorphic infiltrate consisting of CD4-positive T-lymphocytes which show characteristically exocytoses in the epidermis with subsequent formation of Pautrier's microabscesses. The disease may progress with spread to the regional lymph nodes where lymphomata develop. Treatment is initially local with employment of chlormethin ("nitrogen mustard gas") and this treatment can maintain the patients in remission for prolonged periods. In cases with spread to lymph glands or in particularly aggressive forms with tumour formation in the skin, combined chemotherapy is administered (prednisone, cyclophosphamide, etretinate and bleomycin). Thirty-eight of the patients were in stage I in which a clinical suspicion of mycosis fungoides was present but where the histological changes were insufficient to confirm the diagnosis. IVa and ten in stage IVb. The age at the onset of the symptoms was from 59 to 64 years (median values) for the various stages. Stages I and II had approximately 80% five-year survival, while the stages with more extensive spread had approximately 50% survival. The etiology of the disease is unknown but, during recent years, certain evidence has been found suggesting that activation of a retrovirus in the epidermis may be a contributory factor.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed1990

Interferon alpha and etretinate combination treatment of cutaneous T-cell lymphoma.

Eleven patients suffering from cutaneous T-cell lymphoma (mycosis fungoides) were treated with recombinant interferon alpha-2A in combination (seven patients) or alone. Two patients, one in combined treatment, went into clinical complete remission, and five experienced partial remission. Two patients progressed during therapy, and two were nonevaluable because they stopped treatment early due to side effects. Dosages of interferon were from 3 to 36 million units daily for 3 months, and thereafter 3 times weekly. Etretinate (0.7 mg/kg) was given orally. The study showed that recombinant interferon alpha-2A in combination with etretinate or alone can induce remission of cutaneous T-cell lymphoma.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed1990

Time-course studies of immediate and delayed immune reactivity in patients with atopic dermatitis treated with herbal drugs.

We followed a number of in vitro parameters in nine adult patients with atopic dermatitis for a period of 3 weeks during which the patients took herbal drugs that are claimed to improve chronic eczema. The following investigations were performed weekly: blood leucocytes, circulating eosinophils, serum IgE, mitogen responsiveness of lymphocytes, interleukin 1 release, soluble interleukin 2 receptor levels in serum, and in vitro histamine release from basophils in blood. The study demonstrated increased levels of IgE in six patients, increased levels of soluble interleukin 2 receptor in six patients, and a significant correlation between the amount of IgE in serum and the maximal release of histamine from basophils in blood. In this open study five patients experienced a clinical worsening of their disease during the intake of herbal medicine. All other parameters were within normal levels. There was no significant change in the in vitro parameters during the observation period.

Adolescent↗
PubMed1990

Interleukin-1 release from peripheral blood monocytes and soluble interleukin-2 and CD8 receptors in serum from patients with atopic dermatitis.

In 31 adult patients with atopic dermatitis, the capacity to secrete interleukin-1 (IL-1) from peripheral blood mononuclear cells and from purified monocytes was investigated following stimulation with lipopolysaccharide. We also measured soluble interleukin-2 receptor levels (sIL-2R) and CD-8 receptor in serum from some of the patients in order to estimate the degree of lymphocyte stimulation in vivo. We observed that purified monocytes from patients with atopic dermatitis released more IL-1 than unseparated blood mononuclear cells did and also had significantly greater IL-1 activity than non-atopic donors. Addition of histamine in concentrations of 10(-7) to 10(-4) M did not suppress, but rather augmented the IL-1 activity release. An increased monocyte-IL-1 release could lead to increased T lymphocyte activity. We observed that 60% of the patients had increased sIL-2R concentrations in serum. There was no correlation between serum IgE and sIL-2R. Our observations indicate that monocytes in atopic dermatitis patients release increased quantities of IL-1, supporting an augmented T lymphocyte activation in the patients.

Adult↗
PubMed1990

Intralesional interferon-alpha 2b treatment of basal cell carcinoma.

Ten patients with histologically proven basal cell carcinoma were treated with sublesional injections of interferon-alpha 2 b (Introna), 1.5 x 10(6) units per injection, three times per week for 3 weeks. Six of the treated lesions cleared completely without further therapy. These lesions measured less than 19 x 19 mm. There was no relapse during an observation period of up to 21 months. Non-healing tumours were large (greater than 20 x 20 mm) and two of them were of nodular type. Side effects were negligible, if present at all. Introna seems to offer a valuable alternative treatment for selected cases of basal cell carcinoma, when excision or X-ray therapy cannot be performed.

Adult↗