Influence of histamine on the expression of CCL20 in human gingival fibroblasts.

BACKGROUND AND OBJECTIVE: Histamine plays an important role during allergic and inflammatory reactions, and it has been suggested to influence periodontal inflammation. The aim of this study was to investigate the effects of histamine on the expression of the antimicrobial peptide C-C chemokine ligand 20 (CCL20) in human gingival fibroblasts (HGFs) when exposed to toll-like receptor (TLR) agonists. MATERIAL AND METHODS: Monolayers of HGFs from three different donors were exposed to histamine, alone, and in combination with Pam3CSK4 (a TLR2 agonist) or lipopolysaccharide (LPS) from Escherichia coli (a TLR4 agonist), for 2, 4, 6 or 12 h. In another experimental group, cells were pretreated with a specific histamine-1 receptor antagonist (H1R) antagonist, cetirizine. Real-time PCR analysis was performed to detect expression of glyceraldehyde-3-phosphate dehydrogenase (GAPDH), CCL20 and interleukin-8 (IL8) genes. The levels of CCL20 and IL-8 protein were determined by ELISA. RESULTS: In HGFs, histamine induced expression of CCL20 and IL8 genes in a time-dependent manner (p < 0.05). Combined stimulation with histamine and Pam3CSK4 or LPS led to a significant amplification in expression of CCL20 and IL-8 when compared with treatment with each stimulant alone (p < 0.05), and this effect was mediated via pathways involving the H1R (p < 0.05). CONCLUSION: The results of this study suggest a sensitizing effect of histamine on early innate immune responses of HGFs when simultaneously exposed to bacterial virulence factors.

Multiple basal cell carcinomas after long-term exposure to hydrazine: case report and review of the literature.

Hydrazine (N(2)H(4)) is a clear, inorganic colourless liquid. It is known to be a skin sensitizer, a corrosive agent and it causes dermatitis on contact. Hydrazine is employed in chemical plants, used as a corrosion inhibitor for feed waters and may be added to rocket fuels. The authors report the case of a 68-year-old man with multiple basal cell carcinomas (BCCs) covering his arms and face. The patient worked in a steam power plant with extensive exposure to hydrazine for a period of over 10 years. The present case report strongly suggests that there may be a correlation between the long-term exposure to hydrazine and an increased risk for multiple BCCs.

Plantar erythrodysesthesia caused by antiretroviral treatment: a case report and review of the literature.

Palmoplantar erythrodysesthesia is an uncommon localised cutaneous reaction to certain chemotherapeutic agents and characterized by painful palmoplantar erythema and dysesthesia. To the best of our knowledge, we report the first case of plantar erythrodysesthesia in a 40-year-old male patient receiving an antiretroviral combination therapy for HIV.

No effect of anti-interleukin-5 therapy (mepolizumab) on the atopy patch test in atopic dermatitis patients.

BACKGROUND: The atopy patch test (APT) is an in vivo model to study the induction of eczema by inhalant allergens in atopic dermatitis (AD) patients. Mepolizumab is a monoclonal antibody to interleukin-5, which reduces peripheral blood eosinophils. Previously, we reported that mepolizumab treatment did not result in clinical improvement in AD. The current study investigates the effect of mepolizumab therapy on the APT in the same patients. METHODS: Mepolizumab treatment was given at days 0 and 7 in a double-blind placebo-controlled design. The APT was applied at days -2, 0, 14 and 28. Clinical evaluation of each APT was conducted 48 h after application at days 0, 2, 16 and 30. Skin biopsies were taken at days 0, 2 and 16 for eosinophil counts. RESULTS: The mepolizumab-treated group showed no significant reduction in macroscopic outcome of the APT. Tissue eosinophils were reduced in the mepolizumab-treated group at day 16 compared with placebo; however, this was not significant. CONCLUSION: Mepolizumab therapy cannot prevent the eczematous reaction induced by the APT. Furthermore, the influx of tissue eosinophil numbers in the APT is not significantly inhibited after mepolizumab treatment compared with placebo, despite a significant reduction in peripheral blood eosinophils.

Anti-IL-5 recombinant humanized monoclonal antibody (mepolizumab) for the treatment of atopic dermatitis.

BACKGROUND: Eosinophils may play an important role in the pathogenesis of atopic dermatitis (AD). Interleukin-5 is essential for eosinophil growth, differentiation and migration. A monoclonal antibody to human interleukin-5 (mepolizumab) was developed for atopic diseases. This study was designed to study the effect of mepolizumab in AD. METHODS: Two single doses of 750 mg mepolizumab, given 1 week apart, were studied in patients with moderate to severe AD using a randomized, placebo-controlled parallel group design. The primary endpoint of 'success' to treatment was defined as the percentage of patients with at least 'marked improvement' after 2 weeks as assessed by the Physician's Global Assessment of Improvement (PGA). Furthermore, SCORing AD (SCORAD), pruritus scoring, number of blood eosinophils and serum thymus and activation-regulated chemokine (TARC) values served as secondary endpoints. Fluticasone propionate cream 0.05%, once daily could be used as rescue medication from day 16 if no improvement was recorded. RESULTS: Eighteen patients received mepolizumab and 22 placebo treatment. Peripheral blood eosinophil numbers were significantly reduced in the treatment group compared with placebo (P < 0.05). No clinical success was reached by PGA assessment (P = 0.115), SCORAD (P = 0.293), pruritus scoring and TARC values in the mepolizumab-treated group compared with placebo. However, modest improvement (<50% improvement) assessed by PGA was scored significantly more in the mepolizumab-treated group compared with placebo (P < 0.05). CONCLUSION: Two single doses of 750 mg mepolizumab did not result in clinical success in patients with AD, despite a significant decrease in peripheral blood eosinophils.

Proteus syndrome with widespread portwine stain naevus.

Proteus syndrome is a rare condition comprising asymmetrical overgrowth of different parts of the body in association with various cutaneous abnormalities. We describe a 3-year-old boy with Proteus syndrome, who presented with hemihypertrophy of the right leg, asymmetric macrodactyly, subcutaneous masses and a widespread portwine stain interspersed with angiokeratomas on the right leg, scrotum and on the middle and left side of the back. Doppler ultrasound of the right leg did not show hypercirculation, but did reveal the absence of the right superficial femoral vein.

The Dyshidrotic Eczema Area and Severity Index - A score developed for the assessment of dyshidrotic eczema.

BACKGROUND: Dyshidrotic eczema of the palms and soles is a common condition, which can be rather resistant to treatment. Therapy studies and their comparability are of clinical importance. OBJECTIVE: As standardized assessment methods for the severity of this particular form of eczema are lacking, we developed a severity index for dyshidrotic eczema. METHODS: The Dyshidrotic Eczema Area and Severity Index (DASI) is based on the severity grade of single items - number of vesicles per square centimetre (V), erythema (E), desquamation (S) and itch (I) - and the extension of the affected area (A) and is calculated with defined score points (p) as: DASI = (pv + pE = pS + pI) x pA. RESULTS: In two treatment studies on dyshidrotic hand eczema, the DASI was found to be a simple and useful tool to assess the severity of dyshidrotic eczema and the effect of therapy. CONCLUSION: The DASI needs to be further validated in larger cohorts.

[Eosinophilic cellulitis (Wells syndrome)]. / Eosinophile Zellulitis (Wells-Syndrom).

Eosinophilic cellulitis (Wells' syndrome) is a rare disorder characterized clinically by recurrent erythematous plaques resembling cellulitis and histologically by a dermal infiltrate of lymphocytes, eosinophils and eosinophil debris between collagen bundles, forming flame figures in typical cases. A 71-year-old woman with Wells' syndrome with blood and bone marrow eosinophilia showed a good response to dapsone. The level of eosinophil cationic protein (ECP) in serum was elevated. Immunophenotyping of peripheral T cells revealed an increased proportion of CD3+CD4+T cells. The patients' cultured peripheral lymphocytes spontaneously released significant amounts of interleukin 5 (IL-5), but not interleukin 4 (IL-4) or interferon gamma (IFN gamma). These findings suggest that activated T cells may be involved in the pathogenesis of blood and tissue eosinophilia in this patient.

Abnormal clones of T cells producing interleukin-5 in idiopathic eosinophilia.

BACKGROUND: The cause of persistent eosinophilia and the hypereosinophilic syndrome is unknown. Recent work suggests that in some patients with the hypereosinophilic syndrome, a clone of abnormal T cells produces large amounts of interleukin-5, a cytokine required for the growth and differentiation of eosinophils. We examined T-cell surface markers, rearranged T-cell-receptor genes, and in vitro production of cytokines by T cells from patients with idiopathic eosinophilia. METHODS: The expression of surface molecules on T cells was measured by flow cytometry. Cytokine expression was measured by enzyme-linked immunosorbent assay, flow cytometry, and immunohistochemical analysis. To identify dominant (clonal) rearrangements of the T-cell receptor within the lymphocyte population, Southern blot analysis (beta chain) and the polymerase chain reaction (gamma chain) were performed according to standard protocols. RESULTS: Among 60 patients with idiopathic eosinophilia, 16 had circulating T cells with an aberrant immunophenotype. In each of these patients, the abnormal immunophenotype was unique. Evidence of clonal rearrangements of the T-cell receptor was obtained in 8 of the 16 patients. In most instances, the abnormal T cells expressed large amounts of surface proteins associated with T-cell activation (the alpha chain of the interleukin-2 receptor and the HLA-DR antigen). Moreover, the aberrant T cells produced large amounts of interleukin-5 in vitro. CONCLUSIONS: Clonal populations of abnormal T cells producing interleukin-5 occur in some patients with idiopathic eosinophilia.

Clinical and immunological features of patients with interleukin-5-producing T cell clones and eosinophilia.

Recent work suggests that in some patients with the hypereosinophilic syndrome, a clone of abnormal T cells produces large amounts of interleukin-5. In this study, we examined 60 patients with idiopathic eosinophilia. Sixteen patients had circulating T cells with an aberrant immunophenotype that, in most cases, were associated with different forms of skin inflammation. The abnormal T cells produced large amounts of interleukin-5, which may have increased eosinophil differentiation in the bone marrow of these patients.

The interaction of human peripheral blood eosinophils with bacterial lipopolysaccharide is CD14 dependent.

Bacterial lipopolysaccharide (LPS, endotoxin) is a ubiquitous component of dust and air pollution and is suspected to contribute after inhalation to an activation of eosinophils in bronchial tissues of asthmatic patients, provoking inflammatory and allergic processes. We were therefore interested in the interaction of eosinophil granulocytes with LPS and have examined the activation of and uptake to human peripheral blood eosinophils by LPS. Eosinophils were stimulated by LPS and the endotoxic component lipid A and the release of tumor necrosis factor alpha (TNF-alpha) and of the eosinophil-specific granule protein eosinophil cationic protein (ECP) was estimated. The results show induction of TNF-alpha and ECP-release by LPS and lipid A in a dose-dependent manner. Anti-CD14 monoclonal antibody (moAb) (clone MEM-18) and the synthetic lipid A partial structure 406 blocked the release of TNF-alpha and ECP by LPS-stimulated eosinophils. Studies with radioactively labeled LPS showed dose-dependent uptake of (3)H-LPS to eosinophils. The (3)H-LPS uptake was found to be specific because preincubation with unlabeled LPS, compound 406 and also anti-CD14 antibodies inhibited uptake of (3)H-LPS to eosinophil granulocytes. By flow cytometry using anti-CD14 moAb and by reverse transcriptase-polymerase chain reaction (RT-PCR) technique, CD14 expression was detectable. Furthermore, messenger RNA (mRNA) expression of Toll-like receptors (TLR) 2 and TLR 4 was detected, indicating the presence of these CD14 coreceptors. The results indicate that eosinophils can take up LPS and can be stimulated by LPS in a CD14-dependent manner. Hence, in addition to allergens, eosinophils interact with endotoxin, a process that possibly exacerbates ongoing inflammatory and allergic processes.