Reduction of leukotriene B4-induced intraepidermal accumulation of polymorphonuclear leukocytes by methotrexate in psoriasis

Lammers, A.M.; Kerkhof, Peter C M van de; Mier, P.D.

doi:10.1111/j.1365-2133.1987.tb05900.x

Cited by 26 publications

(5 citation statements)

References 8 publications

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“…In addition, MTX decreases the neutrophil and monocyte chemotaxis, 17 and inhibits the leukotriene B4‐induced penetration of neutrophils 18 . Via interference with the vitamin D receptor, calcipotriol stimulates cellular differentiation, inhibits proliferation and plays an important part in immune modulation 19–21 …”

Section: Discussionmentioning

confidence: 99%

The combination of calcipotriol and methotrexate compared with methotrexate and vehicle in psoriasis: results of a multicentre placebo-controlled randomized trial

et al. 2003

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Section: Discussionmentioning

confidence: 99%

The combination of calcipotriol and methotrexate compared with methotrexate and vehicle in psoriasis: results of a multicentre placebo-controlled randomized trial

et al. 2003

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“…LTB 4 is a highly specific leucocyte chemoattractant that is naturally present in lesional psoriatic skin. Epicutaneous application of LTB 4 induces artificial intra‐epidermal PMN accumulation with well‐established time and phase intervals . However, to the best of our knowledge, no real‐time in vivo studies have been performed so far that evaluate the dynamics of leucocyte accumulation in psoriasis or any inflammatory skin disease.…”

Section: Introductionmentioning

confidence: 99%

Establishing the dynamics of neutrophil accumulation in vivo by reflectance confocal microscopy

Wolberink

Peppelman

Kerkhof

et al. 2014

Experimental Dermatology

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Reflectance confocal microscopy (RCM) is an imaging tool, which visualizes the epidermal skin layers in vivo with a cellular resolution. Neutrophil accumulation is a characteristic feature in psoriasis and is thought to play a role in the pathophysiology of psoriasis. Until now, imaging of neutrophil accumulation in vivo is not performed. We evaluated the dynamics of neutrophil migration in active psoriatic lesions by non-invasive RCM imaging. Additionally, we evaluated the time phasing and duration of neutrophil trafficking. We performed RCM imaging prior to the start of topical treatment and for seven consecutive days with a 24-h time interval at the Radboud University Medical Center, Nijmegen, the Netherlands. Twelve psoriatic lesions in three patients with a severe exacerbation of psoriasis were included. The four most active lesions were selected in each patient based on the highest degree of redness, induration and expansion in the previous 2 weeks. In all lesions, a cyclic pattern of neutrophil migration was observed, consisting of squirting papillae, transepidermal migration, accumulation in the stratum spinosum, accumulation in the stratum corneum and degeneration of the abscesses. The time interval of a neutrophil-trafficking cycle was 5-7 days and showed a synchronic time phasing. This study is the first to establish the dynamics and time phasing of neutrophil migration in vivo in psoriatic lesions. Previously reported theories were confirmed by these novel in vivo data. RCM might distinguish between active or chronic psoriatic areas, which might contribute to new insights into the pathogenesis of psoriasis.

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“…However methotrexate had an inhibitory effect on two functions of interleukin 1 in vitro. Several other studies suggest that neutrophil chemotaxis is depressed in the presence of methotrexate, indicating a direct or indirect effect of methotrexate on neutrophils with positive consequences on psoriatic lesions (39)(40)(41). Johnson et al (42) demonstrated in an adjuvant arthritis rat model that methotrexate, indomethacin and prednisolone are efficient antiinflammatory drugs, but only methotrexate had the ability to prevent systemic activation and local accumulation of inflammatory cells, whereas indomethacin and prednisolone suppressed only the ongoing local inflammatory process.…”

Section: Discussionmentioning

confidence: 96%

Mechanism of Action of Methotrexate: Experimental Evidence that Methotrexate Blocks the Binding of Interleukin 1β to the Interleukin 1 Receptor on Target Cells

Brody¹,

Böhm²,

Bauer³

1993

Clinical Chemistry and Laboratory Medicine

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Interleukin 1, a multifunctional cytokine, plays a central role in inflammatory processes and induction of the immune response. Target cells possess 200 -5000 (or more) interleukin 1 receptors per cell, but they exhibit a full biological response when only 1 -2% of these receptors are occupied by interleukin la or I . Methotrexate has been reported to be beneficial in several inflammatory and autoimmune diseases. On the other hand, many of these diseases are known to share an overproduction of interleukin 1. It has been demonstrated that methotrexate has no influence on the interleukin 1 synthesis, so we focused our attention on the ability of methotrexate to interfere with the binding of interleukin 1 β to the interleukin 1 receptor. The experiments were performed on monocytes, lymphocytes and granulocytes using a recombinant human cytokine probe. Methotrexate led to an astonishing decrease in the binding of interleukin 1 β to the interleukin 1 receptor of peripheral blood cells, whereas methylprednisolone and indomethacin were not inhibitory. The inhibitory effect of methotrexate was dose dependent. An excess of interleukin I abolished the inhibition of cytokine binding by methotrexate. We also demonstrated that methotrexate does not affect the integrity of the interleukin 1 receptor or of the target cells. Our results demonstrate that methotrexate blocks the interleukin l -interleukin 1 receptor pathway. Methotrexate is therefore another interleukin 1 inhibitor and a clinically efficient anticytokine. but exert a full biological effect when only 1 -2% of Interleukin 1 is represented by two distinct cytokines, these receptors are occupied by interleukin 1 (2). interleukin la and interleukin I polypeptides, which ^ ,11·,.,

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Reduction of leukotriene B4-induced intraepidermal accumulation of polymorphonuclear leukocytes by methotrexate in psoriasis

Cited by 26 publications

References 8 publications

The combination of calcipotriol and methotrexate compared with methotrexate and vehicle in psoriasis: results of a multicentre placebo-controlled randomized trial

The combination of calcipotriol and methotrexate compared with methotrexate and vehicle in psoriasis: results of a multicentre placebo-controlled randomized trial

Establishing the dynamics of neutrophil accumulation in vivo by reflectance confocal microscopy

Mechanism of Action of Methotrexate: Experimental Evidence that Methotrexate Blocks the Binding of Interleukin 1β to the Interleukin 1 Receptor on Target Cells

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