Klas Nordlind

• Karolinska University Hospital

Background Atopic dermatitis (AD) is a chronic inflammatory skin disorder characterized by eczematous lesions, dry skin and persistent itch. AD may worsen due to psychological stress. However, little is known about the neural correlates that mediate the interaction between psychological stress and AD. Objectives To identify the possible difference...

Background Atopic dermatitis (AD) is a chronic inflammatory skin disorder. It is often reported to be worsened by psychological stress. Objective To explore the role of psychological stress and related triggers in AD, and its connection to worsening of this disease, focusing on patients’ perspectives. Methods In total, 28 patients with AD were in...

Background: Atopic dermatitis (AD) is a chronic, inflammatory, often severely itching skin disorder. It may worsen due to stress, depression, or anxiety. Calcitonin gene-related peptide (CGRP) may be involved in inflammation signaling. CGRP has also been suggested in relation to stress, depression, and anxiety. This study aimed to investigate the...

Psoriasis is a chronic inflammatory skin disease that may be triggered or worsened by several factors, including alcohol. A higher than average alcohol consumption is common among individuals with psoriasis. Neurobiological signaling affected by alcohol intake includes a range of neurotransmitters, such as the dopaminergic, serotonergic, and tachyk...

Context: Atopic dermatitis (AD) is a chronic, inflammatory, itching skin disorder, which may worsen due to stress, depression and anxiety. Tachykinins may be involved in inflammation signaling as well as they may have a role in stress, depression and anxiety. Objective: This study aimed to measure the expression of tachykinin markers, in the skin o...

Background Chronic prurigo (CPG) is a distinct disease characterized by chronic pruritus, history and/or signs of prolonged scratching and multiple pruriginous lesions. It may present with various clinical manifestations, including papules, nodules, plaques or umbilicated lesions. Some patients with chronic pruritus show pruriginous linear and scar...

Atopic dermatitis (AD) is a chronic, itchy, inflammatory skin disorder that may worsen due to stress and anxiety. Tachykinins have been suggested to be involved in the inflammation in AD, as well as pruritus, stress and anxiety. Aprepitant is a NK-1 receptor antagonist. This open randomized trial evaluated the effect of aprepitant added to topical...

Psoriasis has been reported to be associated with alcohol consumption. To investigate the level of alcohol intake in individuals with psoriasis and correlate intake with the extent of disease and pruritus. Twenty-nine outpatients (15 females and 14 males) with stable chronic plaque psoriasis of moderate severity were recruited. The Psoriasis Area a...

Stress and anxiety may worsen atopic dermatitis (AD) through the serotonin system. Serotonergic expression was measured in 28 patients with AD in relation to extent of the disease (SCORing of Atopic Dermatitis; SCORAD), pruritus intensity (visual analogue scale; VAS), anxiety traits (Swedish Universities Scales of Personality; SSP) and depression (...

Physical activity promotes health and prevents disease. When patients with atopic dermatitis (AD) undertake exercise, the itch often gets worse due to sweating, and this may reduce their engagement in physical exercise. The aim of this study was to determine the level of physical exercise in patients with AD compared with a control group from a nor...

To investigate whether psoriasis is affected by the use of serotonin reuptake inhibitors (SSRIs). A population-based cohort study. The general adult population with plaque psoriasis in Sweden between 1997 and 2006. A total of 69 830 patients with plaque psoriasis were identified in the National Patient Register. Whether study subjects were exposed...

Atopic eczema symptoms may worsen due to stress. In the present study, the cerebellar cortex of the atopic-like mouse NC/Nga was studied regarding the effect of chronic mild stress on expression of two well-characterized serotonergic receptors (R), 5-HT1A and 5-HT2A. In total 24 mice were used. Sixteen of these mice were subjected to unpredictable...

Atopic dermatitis (AD) is a chronic inflammatory skin disease with often severe itch. The aim of this study was to determine the pruritogenic and vascular effect of serotonin (5-hydroxytryptamine; 5-HT) in patients with AD and in healthy controls. A 50 µg dose of 5-HT was injected intradermally into non-lesional skin of 25 patients with AD and 25 h...

Psoriasis may be worsened by stress and mood disorders. There is an increased expression of the serotonin transporter protein (SERT) in involved psoriatic skin as compared to non-involved psoriatic skin and normal skin. The aim of this study was to investigate if the increased expression of SERT in psoriasis correlates with the severity of disease,...

Human mastocytosis is a rare disease, in which the serotonergic system may be involved. The objective of the present study was to examine the possible presence of serotonin (5-HT) and its 5-HT1A receptor (R) in the skin of patients with mastocytosis. In addition, the effect of the 5-HT1AR was tested on human mastocytosis cells, cultured in vitro. T...

Background Stress is known to worsen the symptoms of atopic eczema (AE). Substance P is likely to play an important role in the development and pathogenesis of AE. Objective To examine a possible connection between chronic mild stress and changes in the expression of substance P and its receptor (R) neurokinin (NK) 1 in the skin and stress-related...

The symptoms of atopic dermatitis (AD) are often aggravated by anxiety, and the serotonin transporter (5-HTT) has been shown to be of importance in this context. Three polymorphisms affecting transcription of this gene are known: a repetitive element, in the promoter region (5HTTLPR), a variable number tandem repeats (VNTR) within intron 2 referred...

Atopic eczema is often worsened by stress. While acute stress is associated with increased turnover of serotonin (5-hydroxytryptamine; 5-HT), chronic stress causes a decrease. In chronic stress, there is a decrease of the 5-HT1A receptor (R)- and an increase in the 5-HT2AR-responsiveness to 5-HT. In the present study, the impact of chronic mild str...

BACKGROUN: Various mediators of pruritus have been suggested that might be responsible for the mechanism of pruritus in psoriasis. To study the expression levels of members of the tachykinin family, substance P and neurokinin (NK) A and their receptors, NK-1 and NK-2, in psoriasis and to correlate their expression with the intensity of pruritus. A...

The neuromediator serotonin (5-hydroxytryptamine; 5-HT) has been proposed to play a role in tumor progression. Thus, the aim of the present investigation was to determine whether alterations in the serotonergic system occur in nevomelanocytic tumors. For this purpose, paraffin-embedded biopsies of superficial spreading malignant melanoma (SSM), dys...

Psoriasis is a chronic inflammatory disease in which pruritus is a common symptom. Pruritus may be associated with the gamma-aminobutyric acid (GABA) system. The distribution of GABA and its GABA(A) receptor (R) was studied in involved and non-involved psoriatic skin, as well as normal healthy control skin, using an immunohistochemistry technique....

Background: Various mediators have been suggested for the pathogenesis of pruritus in psoriasis. Methods: To investigate cutaneous responses of substance P in pruritic lesional and nonlesional areas of psoriasis patients and in healthy controls, substance P, saline and histamine were injected intradermally. After each injection, pruritus, flare...

A connection between chronic mild stress and altered innervation in the skin of an atopic mouse strain, NC/Nga, was studied. We used three groups of mice, stressed control (SC, stressed but not immunized with a mite antigen), non-stressed eczematous (NSE, not stressed but immunized) and stressed eczematous (SE, stressed and immunized). There was a...

Mast cells of a number of different animal species have been reported to contain serotonin (5-hydroxytryptamine; 5-HT), a monoamine capable of numerous and complex actions, which may include an impact on tumour growth. Limited previous studies have suggested that normal or neoplastic canine mast cells do not express 5-HT. In the present study, cani...

The nervous system contributes to inflammatory skin diseases. Objective The aim of this investigation was to study the neuronal contribution to psoriasis at the remission and exacerbation phases. We examined the expression of the neuronal markers protein gene product 9.5 (PGP 9.5), growth-associated protein-43 (GAP-43) and substance P, in addition...

Since the symptoms of psoriasis may be changed by treatment with selective serotonin reuptake inhibitors (SSRIs), the expression of serotonin (5-HT) and its transporter protein (SERT) in the skin of patients with psoriasis were examined employing a biotinylated-streptavidine procedure. In biopsies of such skin staining for 5-HT was limited to plate...

Pruritus in psoriasis patients has not been regarded as a major symptom. Objective To study the pattern of pruritus in chronic plaque psoriasis. A questionnaire was sent out to 109 patients with a diagnosis of chronic plaque psoriasis, who attended our outpatient departments during the period of January 2006 to January 2007. Out of 109 patients, 80...

Psoriasis is generally thought to be worsened by stress. This presumption has been supported primarily by retrospective studies using questionnaires. No controlled prospective study on this issue has been performed. Nine women with moderate plaque psoriasis were enrolled in the study. They all believed that their psoriasis was worsened by stress. T...

Serotonin (5-hydroxytryptamine; 5-HT) is an important mediator of bidirectional interactions between the neuroendocrine system and the skin. The rate of synthesis of 5-HT from l-tryptophan can be enhanced by brain-derived neuronal growth factor, cytokines, exposure to ultraviolet light and steroids. The major source of 5-HT in the skin are platelet...

Pruritus is a common complaint among patients of psoriasis vulgaris of the chronic plaque type. Despite a high prevalence of pruritus in psoriasis, limited information is available on this subject. The aim was to assess patients' perspective of pruritus in psoriasis vulgaris of plaque type, by using focus groups. A total of 20 patients with chronic...

To identify pathoaetiological neuroimmune mechanisms in patients with atopic dermatitis (AD) and chronic stress, focusing at nerve density, sensory neuropeptides, and the serotonergic system. Eleven patients with AD with histories of stress worsening were included. Biopsies from involved and non-involved skin were processed for immunohistochemistry...

Psoriasis is a chronic inflammatory skin disease, where specific immunity and/or innate immunity may be of importance in the disease pathogenesis. Psoriasis may be worsened by stress, which suggests that a neuroimmune interaction is contributing to the disease. Serotonin (5-HT) is a monoamine which besides general effects also has an impact on cell...

Serotonin (5-hydroxytryptamine, 5-HT) was proposed to modulate murine contact allergy by binding to 5-HT(1A/2A) receptors (R). We examined the expression of 5-HT(2C)R in the skin of mice with contact allergy, as well as the effects of an agonist and antagonist of this receptor on the elicitation phase of this type of allergy. Immunohistochemistry r...

Expression of serotonin (5-hydroxytryptamine; 5-HT), 5-HT receptors 1A (5-HT1AR) and 2A, and serotonin transporter protein (SERT) was studied in positive epicutaneous reactions to nickel sulphate in nickel-allergic patients, at 72 h post-challenge with the antigen. In addition, the effects of 5-HT2AR agonist 2,5-dimethoxy-4-iodoamphetamine (DOI), a...

Substance P and its receptor(R) neurokinin (NK)-1 may have a role in the pathogenesis of psoriasis. Stress has been reported to play a role in the onset and exacerbation of psoriasis, which might include the substance P-NK-1 receptor(R) pathway. A feature of psoriasis, that has been correlated to the severity of stress and secretion of substance P,...

Nerve fibers and sensory neuropeptides substance P and calcitonin gene-related peptide (CGRP) have been reported to be involved in allergic contact dermatitis (ACD). In the present study, we investigated the general innervation (using antibody against protein gene product 9.5, PGP 9.5), axonal growth (using antibody against growth associated protei...

Psoriasis appears to be influenced by stress, which causes release of adrenal hormones. Serotonin, or hormonal actions on serotonin and serotonin receptors, may have a role in psoriasis. Distribution of serotonin receptors was studied in involved and noninvolved skin in patients with psoriasis and compared to normal skin, by using immunohistochemis...

Density of nerve fibers, axonal growth, calcitonin gene-related peptide (CGRP), and substance P, and serotonin immunoreactivity as well as concentration were all determined in a murine model of contact allergy. Female Balb/c mice were sensitized on the back with oxazolone and 6 days later challenged with the same antigen on the dorsal surface of th...

Patients with atopic dermatitis (AD) often have increased skin sensitivity and this symptom often worsens during stress. We sought to find out whether patients with AD had stinging, and to identify the pathocausal neuroimmune mechanisms, including the role of stress. In all, 25 patients with AD with histories of stress worsening were tested using a...

Galanin is a neuropeptide widely distributed in the nervous system. The expression of galanin was investigated in murine contact allergy using immunohistochemistry, radioimmunoassay and in situ hybridization. Female BALB/c mice were sensitized with oxazolone and 6 days later challenged on the dorsal surface of ears, while control mice received vehi...

To study the effect of laser treatment on rosacea, a common facial skin disease with symptoms of blushing, redness, telangiectasis, papules, pustules, and diffuse swelling of the skin, we focused on the stinging sensation and performed immunohistochemical evaluation of nerve density and neuropeptide expression. Clinical investigation as well as the...

The expression of the serotonin (5-HT) receptors 5-HT1AR, 5-HT2AR and 5-HT3R was investigated in allergic contact eczematous human skin by an indirect fluorescence method. 5-HT1AR expression was found in basal epidermal NK1-beteb-positive cells, which were more elongated and showed longer dendritic processes in contact eczematous skin than in contr...

The expression of heat shock protein (hsp) 65, 72 and 90 was studied in human inflamed skin after heavy metal salt treatment, by using epicutaneous patch-testing procedure and immunohistochemistry. There was a slight immunoreactivity to hsp 65 and hsp 72, but not to hsp 90 in keratinocytes in normal skin. An increased immunoreactivity to hsp 72 was...

A suggested role for nicotine in the pathogenesis of palmoplantar pustulosis (PPP) has been discussed. The target for the inflammation in PPP is the acrosyringium. Nicotine acts as an agonist on nicotinic acetylcholine receptors (nAChRs) and can influence a variety of cellular functions. To study the alpha 3- and alpha 7-nAChR expression in palmar...

Ninety-five percent of patients with palmoplantar pustulosis are smokers at onset of the disease. The aim of this study was to determine whether these patients have serum antibodies to nicotinic acetylcholine receptors (nAChR ab) and if their sera induce a specific immunofluorescence in normal palmar skin. Sera from 45 patients with palmoplantar pu...

Nickel sulphate stimulates the proliferation of lymphocytes in nickel-allergic subjects. However, nickel-induced stimulation of lymphocytes from control persons without clinical symptoms of nickel allergy has also been reported. The aim of the present study was to correlate T cell activity, measured by DNA synthesis and the expression of Th1 [inter...

Peripheral blood mononuclear cells (PBMC) were challenged with different concentrations of mercuric chloride and the expression of heat shock protein (hsp) 65, 72 and 90, were investigated by an indirect peroxidase method as well as the proliferation was measured by uptake of tritiated thymidine into DNA. Hsp 65 immunoreactivity was peripherally lo...

Patients with palmoplantar pustulosis (PPP) frequently report that stress worsens their condition. A study was therefore made of the distribution and number of nerve fibres positive for protein gene product (PGP) 9.5 (a general nerve marker) and nerve fibres with substance P- and calcitonin gene-related peptide-like immunoreactivity in involved ski...

The distribution of choline acetyltransferase (ChAT) and acetylcholinesterase (AChE) in involved skin in patients with palmoplantar pustulosis (PPP) and in normal palmar skin in healthy non-smokers and smokers has been studied by immunohistochemistry, especially in relation to the sweat gland apparatus. The sweat gland and its duct showed ChAT- and...

The expression of Interleukin-6 (IL-6) was studied in normal dorsal root ganglia (DRG) of juvenile and foetal humans, using immunohistochemistry and in situ hybridization techniques. There was an expression of IL-6-like immunoreactivity in more than 75% out of neuronal cells in the juvenile ganglia with a peripheral localization, and also an expres...

The intimate, bidirectional link between neuroendocrine and immune systems is now accepted. A modulating effect of the nervous system on immune and inflammatory responses has been corroborated by identification of neuropeptide receptors on immunocompetent cells and the finding that neuropeptides can regulate leukocyte functions. The present study w...

There is increasing evidence that the nervous system has influence on the immune response. The effect of vasoactive intestinal peptide (VIP) and of serotonin and its antagonists on the challenge phase of allergic contact dermatitis in humans were tested. The substances were injected intracutaneously shortly before and 6 h after application of patch...

Allergic contact dermatitis (ACD) is a common clinical condition leading to considerable morbidity. We have recently demonstrated that ketanserin, a serotonin antagonist, significantly inhibits nickel sulphate-induced ACD. Furthermore, serotonin-immunoreactive (IR) cells have previously been demonstrated in normal human cutaneous melanocytes. To fu...

Vasoactive intestinal polypeptide (VIP) is a neuropeptide with immunomodulatory properties. To elucidate the possible role of VIP in the pathophysiology of cutaneous contact hypersensitivity, we compared involved with uninvolved skin of allergic contact dermatitis (ACD) from nickel-allergic patients. Assays included quantification of VIP-immunoreac...

Nowhere in the body are inflammatory reactions more apparent than in the skin. The inflammation may be beneficial, as in defence against tumours or infections, or inimical, as in allergy and psoriasis. The skin is a primary immunological organ which presents antigens to T cells, and produces many types of cytokines. The complex interplay between ce...

Immunohistochemistry was applied in the investigation of the possible existence of serotonin in human skin. It was found that epidermal melanocytes express a serotonin-like immunoreactivity. The immunoreactivity was associated with both the cytoplasm and the cellular membrane, though the latter was only found in certain cells. The serotonin anti-se...

Nowhere in the body are inflammatory reactions more apparent than in the skin. The inflammation may be beneficial, as in defence against tumours or infections, or inimical, as in allergy and psoriasis. The skin is a primary immunological organ which presents antigens to T cells, and produces many types of cytokines. The complex interplay between ce...

Neuropeptide Y (NPY) concentrations were investigated by radioimmunoassay and immunohistochemistry in a murine model of cutaneous leishmaniasis, using a susceptible (BALB/c) and a resistant (C57BL/6) mouse strain. The analyses were performed on the skin, secondary lymphoid organs and dorsal root ganglia (DRG) at 1, 3, 6 and 9 weeks postinfection. A...

Recruitment, migration and adherence of macrophages and their interaction with inoculated promastigotes are key steps in the initiation of the inflammatory process in cutaneous leishmaniasis. Parasite- and nervous system-derived factors might be involved in this process. In the present study the chemotactic activities of live, killed and sonicated...

The expression of the sensory neuropeptide calcitonin gene-related peptide (CGRP) in the skin, secondary lymphoid organs and dorsal root ganglia (L4-L6) in Leishmania major-induced inflammation was evaluated by radioimmunoassay. The investigation was conducted on two mouse strains, the susceptible BALB/c and the resistant C57BL/6. The CGRP concentr...

The cross-talk between the immune and nervous systems is becoming an interesting field of research and there is accumulating evidence supporting this notion. In the present study we investigated the levels of nerve growth factor in a murine model of cutaneous leishmaniasis, using a two-site ELISA. Two strains of inbred mice were used for this purpo...

There is increasing evidence indicating that the nervous system influences the immune response. In the present study the potential immunomodulatory role of vasoactive intestinal polypeptide (VIP) in established allergic contact dermatitis in humans was investigated. Positive patch-test reactions were elicited by application of nickel sulphate for 4...

Immunoreactivity to interleukin-1 alpha, interleukin-1 beta, interleukin-6 and tumour necrosis factor-alpha and their receptors, as well as the endogenous interleukin-1 receptor antagonist, was investigated in hair follicles in paraffin-embedded normal human skin. Interleukin-1 beta- and tumour necrosis factor-alpha-like immunoreactivities were fou...

Paraformaldehyde-fixed biopsy specimens of normal and chronic cutaneous leishmaniasis human skin were investigated for the presence and cellular distribution of interleukin-1 alpha, interleukin-1 beta, interleukin-6 and tumour necrosis factor-alpha and the corresponding receptors in eccrine sweat glands, using an indirect immunoperoxidase technique...

Interleukin-6-like (IL-6-like) immunoreactivity was sought in inflamed and normal human skin using the same immunohistochemical technique as for detection of neuropeptides. Such immunoreactivity was found in dermal and in a few intraepidermal nerve-like fibres in biopsy specimens from inflamed skin from patients with positive epicutaneous patchtest...

Heavy metal-induced contact eczematous human skin reactions to cobalt chloride and mercuric chloride were investigated for immunoreactivity to interleukin-8 (IL-8), by using an indirect immunoperoxidase staining technique. There was suprabasal epidermal staining for IL-8, with a decrease in the vicinity of areas with parakeratotic epithelium. Howev...

Interleukin-6-like (IL-6-like) immunoreactivity was sought in inflamed and normal human skin using the same immunohistochemical technique as for detection of neuropeptides. Such immunoreactivity was found in dermal and in a few intraepidermal nerve-like fibres in biopsy specimens from inflamed skin from patients with positive epicutaneous patch-tes...

Neuromediators may influence the immune response. To investigate their potential immunomodulating role in established allergic contact dermatitis in man, the following neuromediators were tested: vasoactive intestinal polypeptide (VIP), serotonin, and the serotonin antagonists ketanserin, methiotepine and ICS-205-930. Positive patch test reactions...

Interleukin-1[alpha] and -1[beta], interleukin-6, and tumor necrosis factor-[alpha] may have a protective effect against malignant transformation of melanocytes. By using monoclonal and polyclonal antisera we investigated, in paraformaldehyde-fixed tissue, the cellular distribution of these cytokines in human common and dysplastic nevocellular nevi...

Gamma/delta T cells may act as a first line of defence and respond to stress signals from the surrounding tissue. In the present investigation the occurrence of gamma/delta T cells was studied in the human skin after application of heavy metal salts by a routine epicutaneous patch-testing procedure. Gamma/delta cells were not found in normal skin....

Paraformaldehyde-fixed tissue of chronic granulomatous skin conditions, such as cutaneous leishmaniasis, granuloma annulare, leprosy and hidroadenitis, was investigated for the presence of interleukin-1 alpha-, interleukin-1 beta-, interleukin-6- and tumour necrosis factor-alpha-like immunoreactivities among the cellular infiltrates. There was a we...

The effect of serotonin and the serotonin antagonists ketanserin, methiotepine and ICS-205-930 on the migration of leucocytes was studied by using the sealed capillary migration technique. The migration of mononuclear leucocytes was inhibited by serotonin at 10(-4) and 10(-6)-10(-10)mol/l. An inhibition of the mononuclear leucocyte migration was al...

The value of lymphocyte reactivity in the diagnosis of hypersensitivity to amalgam restorations was studied in a group of patients with oral mucosal lesions, and in a control group. Heavy metal salts were added to lymphocyte cultures, and lymphocyte proliferation and levels of IL-2 receptors and interferon-gamma (IFN-gamma) were determined. After a...

Patients with urticaria pigmentosa were investigated during symptom-free interval regarding plasma concentrations and urinary excretion of immunoreactive regulatory peptides: calcitonin gene-related peptide (CGRP), gastrin, neurokinin A (NKA), neuropeptide Y (NPY), somatostatin (SOM), substance P (SP) and vasoactive intestinal peptide (VIP). The pl...

The presence of glutamate/aspartate-like immunoreactivity was studied in normal human skin and in skin with gold-induced inflammation. In normal skin all epithelial cells were glutamate and, apparently more weakly, aspartate immunoreactive. Both glutamate and aspartate immunoreactivities were also found in macrophage-like, HLA-DR positive cells in...

Patch testing with various metal salts was performed in patients with oral mucosal lesions associated with amalgam restorations, by using polypropylene-coated aluminium discs. Positive reactions to mercuric chloride were obtained in 5/12 (42%) of these patients, but only in 1/11 patients (9%) with oral mucosal lesions unassociated with amalgam rest...

The hormonal neuropeptides calcitonin gene-related peptide (CGRP), cholecystokinin (CCK), neuropeptide Y (NPY) and vasoactive intestinal peptide (VIP), were investigated for a potential protective effect on thymocytes after a toxic dose of nickel sulfate, giving an inhibition of DNA synthesis. There was a statistically significant increase in the s...

The serotonin antagonists ketanserin and methiotepine were tested for a modulating effect on the proliferative response of human peripheral blood T lymphocytes to mercuric chloride. This response was inhibited by ketanserin at 8 x 10(-5) mol/l and by methiotepine at 8.0 x 10(-6) mol/l. There were no additive effects at these concentrations of antag...

This chapter discusses the biological effects of mercuric chloride, nickel sulphate, and nickel chloride. Mercuric chloride, nickel sulphate, and nickel chloride are water-soluble salts. The present knowledge of these compounds regarding metabolism, chemical interactions, and biological effects on different tissues is reviewed. Mercuric chloride ha...