Atsuko Furuta

Effect of histamine H1 receptor antagonists on TARC/CCL17 and MDC/CCL22 production from CD14+ cells induced by antigenic stimulation in vitro.

Background: Thymus- and activation-regulated chemokine (TARC) and macrophage-derived chemokine (MDC) are accepted to be important molecules in the development and maintenance of allergic diseases. Although several types of histamine H1 receptor antagonist (antihistamine) have been developed and used for the treatment of allergic diseases, the influence of antihistamines on TARC and MDC production is not well understood. Objective: The present study was undertaken to examine the influence of antihistamines on TARC and MDC production from CD14+ cells after antigenic stimulation in vitro. Methods: CD14+ cells prepared from patients with pollinosis to Japanese cedar pollen were stimulated with specific allergen extracted from Japanese cedar pollen (Cry j 1) in the presence of azelastine (AZE), ketotifen (KET), fexofenadine (FEX) and oxatomide (OXA) for 6 days. TARC and MDC levels in culture supernatants were examined by ELISA. We also examined the influence of FEX on TARC and MDC mRNA expression, phosphorylation of mitogen-activated protein kinases (MAPKs) and transcription factor activation in CD14+ cells after Cry j 1 stimulation. Results: FEX at 250 ng/ml, which is almost equal to therapeutic blood levels, caused a significant inhibition of TARC and MDC production.However, AZE, OXA and KET required higher concentrations than their therapeutic blood levels to suppress production of these factors. FEX at 250 ng/ml also suppressed NF-ĸB activation, phosphorylation of p38 MAPK and extracellular signal-regulated kinases 1 and 2 and expression of mRNA for TARC and MDC. Conclusions: These results suggest that antihistamines, especially FEX, suppress CC chemokine production from CD14+ cells through interference with antigen-mediated signaling and result in favorable modification of allergic disease states or conditions.

Typical carcinoid tumor arising in the nose and paranasal sinuses—Case report

Carcinoid tumors arise from neuroendocrine cells, many of which are present in the digestive tract and lungs. There have been few reports of carcinoid tumors occurring in the nose and paranasal sinus area, and they are very rare. We encountered a patient with a carcinoid tumor that arose in the nose and paranasal sinuses, and we report the case with a review of the literature. The patient was a 75-year-old woman who began to experience right-sided nasal obstruction, and when her nose began to bleed on the right-side she was examined in our department. A tumor lesion that easily bled and had filled the right nasal cavity was observed. CT revealed a mass lesion with a marked contrast enhancement in the right nasal cavity, ethmoid sinus, and sphenoid sinus, and MRI showed numerous flow voids in the interior that seemed to be tumor blood vessels. The tumor was excised through a lateral rhinotomy. The histopathological diagnosis was a carcinoid tumor. Tumor recurrence was subsequently detected in the vicinity of the opening of the sphenoid sinus, and because the tumor was tending to grow larger, the tumor was resected. The patient has been followed up in the outpatient clinic, recurrence-free.

Suppressive activity of fexofenadine hydrochloride on nitric oxide production in-vitro and in-vivo.

The aim of this study was to examine the effect of fexofenadine hydrochloride (FEX), a histamine H1‐ receptor antagonist, on nitric oxide (NO) production in‐vitro and in‐vivo. Nasal fibroblasts (5 × 105 cells per mL) were stimulated with 25 ng mL−1 tumour necrosis factor‐α in the presence of various concentrations of FEX. NO levels in 24‐h‐culture supernatants were measured by the Griess method and levels of inducible nitric oxide synthase (iNOS) mRNA levels in 12‐h‐cultured cells were measured by ELISA. FEX at more than 0.5 μg mL−1 suppressed NO production from fibroblasts by inhibiting expression of iNOS mRNA. We also examined whether FEX could suppress NO production induced by lipopolysaccharide (LPS) stimulation in‐vivo. BALB/c mice were treated with 5.0 mg kg−1 LPS i.p. after daily oral doses of FEX, 1.0 mg kg−1, for 1–3 weeks. Plasma was obtained 6 h later and NO levels measured by the Griess method. Expression of iNOS mRNA in lung tissues was measured by ELISA 6h after LPS injection. Oral administration of FEX for 2 and 3 weeks, but not 1 week, significantly suppressed NO levels in plasma through the inhibition of iNOS mRNA expression, which were enhanced by LPS stimulation. These results suggest that the attenuating effect of FEX on NO production may be of therapeutic benefit in allergic diseases.

Influence of Histamine H1 Receptor Antagonists on Thioredoxin Production Invitro and In vivo

Background: Thioredoxin (TRX), a 12-kDa oxidoreductase enzyme, is well known to be a redox-active protein that regulates reactive oxidative metabolism. TRX is also accepted to be a protein with anti-inflammatory effects and reported to attenuate the development of allergic airway inflammatory diseases such as allergic rhinitis (AR) and asthma. Although histamine H1 receptor antagonists are frequently used for the treatment of AR, the influence of the agents on TRX production is not well understood. In the present study, we examined the influence of fexofenadine (FEX), cetirizine (CT), and levocetirizine (LCT), which are classified into histamine H1 receptor antagonists, on TRX production in vitro and in vivo. Methods: Macrophages derived from THP-1 cells (1 × 105 cells/ml) were cultured with 50 μM H2O2 in combination with/without the agents for 24 h. Nasal secretions were obtained from patients with Japanese cedar pollen-sensitized rhinitis, who were treated with FEX or LCT for four weeks during pollen season. TRX contents in both culture supernatants and nasal secretions were examined by ELISA. Results: Addition of FEX, CT and LCT into macrophage cultures increased TRX levels in supernatants. The minimum concentration of the agents that caused significant increase was 0.3 μM for FEX, 0.4 μM for CT and LCT. Treatment of patients with FEX and LCT also caused increase in TRX levels in nasal secretions along with attenuation of clinical symptoms. Conclusion: Histamine H1 receptor antagonists may increase the ability of macrophages to produce TRX, and results in favorable modification of clinical conditions of AR.

Basic and clinical immunology – 3021. Inhibitory action of levocetirzine hydrochloride on eosinophil actication in vitro

Methods BALB/c male mice (5 weeks of age) were intraperitoneally infected with 500 Mesocestoides cortii larvae. These mice were then treated with LH at a single dose of 0.1 mg/kg once a day, which was started on the day of infection. The percent of peripheral blood eosinophils and IgE levels were examined 21 days after infection. In the second experiments, eosinophils obtained from mice infected with M cortii were sensitized with M.cortii-specific IgE, and these sensitized eosinophils were stimulated with 10 ng/ml of M. cortii excretory antigen in the presence of LH for 24 h. MIP-1b, LTC4and RANTES levels in culture supernatants were examined by ELISA.

Basic and clinical immunology – 3023. Influence of fexofenadine hydrochloride on uteroglobin production from nasal epithelial cells in vitro and in vivo

Background Uteroglobin (CC10) is well known to be an immuno-suppressive protein secreted from airway epithelial cells after inflammatory stimulation and function in development of allergic disorders. Although histamine H1 receptor antagonists are used for the treatment of allergic disorders, the influence of the agents on CC10 production is not well understood. In the present study, we examined the influence of a histamine H1 receptor antagonist, fexofenadine hydrochloride (FEX) on CC10 production in vitro and in vivo.

Basic and clinical immunology – 3022. Inhibitory action of fexofenadine hydrochloride on mast cell activation in vitro

Background Allergic rhinitis is well known to be accompanied by inflammatory responses in the nasal wall and lumen including predominant infiltration of eosinophils, T cells and mast cells. With the discovery of IgE as the link between allergen exposure and mediator release, mast cells established their role as effector cells in the development and maintenance of allergic diseases. However, the influence of histamine H1-receptor antagonists on mast cells activation is not fully understood. The present study, therefore, was undertaken to examine the influence of histamine H1-receptor antagonist on mast cells activation by using an in vitro cell culture technique and fexofenadine hydrochloride (FEX).