Complementary and alternative medicine for allergic rhinitis in Japan.

BACKGROUND: Complementary and alternative medicine (CAM) is extensively used in patients with allergic diseases worldwide. The purpose of this study was to investigate the actual situation of CAM practice in the treatment of allergic rhinitis. METHODS: We distributed questionnaires to otolaryngologists at 114 facilities in Japan. The subjects who participated in this study included children <16 years of age and adults ≥16 years of age diagnosed with allergic rhinitis by otolaryngologists. The survey was performed in the period from September 2007 to August 2009. Furthermore, we performed the same investigation out of the hospital setting, such as during general health examinations. All questionnaires were returned to Chiba University and analyzed. RESULTS: The proportions of patients who had ever experimented with CAM in the hospital survey were 7.1% (225/3170) and 19.2% (1416/7363) of children and adults, respectively. Approximately 36.2% of the adult patients thought that the treatments were effective. The main reasons for CAM use were safety, convenience and low price. However, the group who spent more than $1000 on CAM felt more dissatisfaction and anxiety related to treatment at the hospital. The situation of CAM practice was not consistent and was instead influenced by the backgrounds of the subjects. CONCLUSIONS: Many patients who receive CAM report feeling that the effects of treatment provided by hospitals are insufficient and have concerns about the side effects of such treatments. Information regarding standard treatments, as described in the guidelines, should become widely known and diffused, and strong communication with patients should be considered.

Characteristics of the Chiba environmental challenge chamber.

BACKGROUND: An environmental challenge chamber (ECC), which we refer to as the α-chamber, was built at Chiba University in 2008. The aim of this study was to validate the functionality of the ECC. METHODS: The stability of the pollen distribution and concentration in the ECC and symptoms of patients with Japanese cedar pollinosis induced by cedar pollen exposure were examined. Carryover effects of symptoms induced by different exposure protocols and correlations between symptoms induced in the ECC and those in the natural cedar pollen season were also determined. All the studies using the α-chamber were conducted out of the cedar pollen season. RESULTS: The severity of symptoms in the chamber reached a peak about 2 hours after the start of pollen exposure and plateaued thereafter. After subjects left the chamber, the symptoms persisted for several days. There was no significant difference between the severity of symptoms at exposure levels of 8000 and 12000 grains/m3. The symptoms were significantly increased by exposure for 3 consecutive days; however, there were no carryover effects in a study performed with a two-week interval. The total nasal symptom score (TNSS) in the natural pollen season showed a weak correlation with the mean TNSS on the day of exposure and the following 3 days. Symptoms in the ECC also had weak correlations with those in the early natural pollen season. CONCLUSIONS: The ECC under well-controlled conditions is suitable for clinical studies and might accelerate development of treatment for seasonal allergic rhinitis. A complete evaluation requires inclusion of the persistent reaction after subjects leave the ECC.

IL-21-induced Bepsilon cell apoptosis mediated by natural killer T cells suppresses IgE responses.

Epidemiological studies have suggested that the recent increase in the incidence and severity of immunoglobulin (Ig)E-mediated allergic disorders is inversely correlated with Mycobacterium bovis bacillus Calmette Guerin (BCG) vaccination; however, the underlying mechanisms remain uncertain. Here, we demonstrate that natural killer T (NKT) cells in mice and humans play a crucial role in the BCG-induced suppression of IgE responses. BCG-activated murine Valpha14 NKT cells, but not conventional CD4 T cells, selectively express high levels of interleukin (IL)-21, which preferentially induces apoptosis in Bepsilon cells. Signaling from the IL-21 receptor increases the formation of a complex between Bcl-2 and the proapoptotic molecule Bcl-2-modifying factor, resulting in Bepsilon cell apoptosis. Similarly, BCG vaccination induces IL-21 expression by human peripheral blood mononuclear cells (PBMCs) in a partially NKT cell-dependent fashion. BCG-activated PBMCs significantly reduce IgE production by human B cells. These findings provide new insight into the therapeutic effect of BCG in allergic diseases.

Sublingual administration of Lactobacillus paracasei KW3110 inhibits Th2-dependent allergic responses via upregulation of PD-L2 on dendritic cells.

Lactic acid bacteria have potential in immunomodulation therapy, but their clinical efficacy and underlying mechanisms are unclear. We aimed to clarify the anti-allergic immune responses induced by intragastric and sublingual administration of heat-killed Lactobacillus paracasei KW3110 and Lactobacillus acidophilus L-92. The KW3110 strain (but not the L-92 strain) enhanced ovalbumin (OVA)-induced expression of CCR-7 and PD-L2 in murine dendritic cells (DCs), and strongly inhibited IL-5 and IL-13 production in vitro in co-cultures with Th2-skewed CD4(+) T cells from DO11.10 transgenic mice. Sublingual administration of low-dose KW3110 (but not L-92) to OVA-sensitized mice selectively suppressed serum IgE production and Th2 cytokine expression in cervical lymph nodes, and significantly improved symptoms after OVA provocation in vivo. KW3110 probably accelerates DC migration into the regional lymph nodes and inhibits Th2 cytokine production through enhanced CCR-7 and PD-L2 expression. Thus, sublingual KW3110 administration may be effective in reducing allergic inflammation.

Association of the MMP9 gene with childhood cedar pollen sensitization and pollinosis.

Matrix metalloproteinase 9 (MMP9) gene has been shown to be involved in the pathogenesis of allergic rhinitis (AR) and asthma. Previous studies suggested that single-nucleotide polymorphisms (SNPs) of the MMP9 gene conferred a risk for childhood asthma. However, whether the SNPs confer a risk for AR has not been previously investigated. The objective of this study was to investigate whether SNPs of the MMP9 gene are associated with risk of seasonal AR (pollinosis), perennial AR and allergen sensitization. A total of 670 school children were recruited in Japan and genotyped for functional polymorphism in the promoter (-1590C/T: rs3918242) and three amino-acid substitutions (R297Q: rs17576; P574R: rs2250889; R668Q: rs17577). Serum levels of total and specific IgE were determined. Disease status and other clinical characteristics of the subjects were investigated using a questionnaire. Associations between the MMP9 SNPs and both AR and serum IgE levels were evaluated. -1590C/T showed significant association with cedar pollinosis (corrected P (Pcor)=0.039). R668Q was in strong linkage disequilibrium (LD) with -1590C/T and showed significant association with cedar pollinosis (Pcor=0.023) and serum cedar pollen-specific IgE level (Pcor=0.022). A haplotype associated with -1590T and 668Q showed a significant association with cedar pollinosis, orchard grass pollinosis and cedar pollen-specific IgE (Pcor=0.0012, Pcor=0.0059 and Pcor=0.0041, respectively). R297Q and P574R were in weak LD with the rest of the SNPs and did not show significant association with disease. Compared with wild-type MMP9 protein (279R-574P-668R), a variant enzyme (279R-574P-668Q) that showed association with pollinosis had lower activity. However, lower enzyme activity was not associated with disease risk because another variant (279Q-574R-668R) showed lower enzyme activity but was not associated with pollinosis. The -1590T allele and its corresponding haplotype was associated with higher promoter activity and with pollen-specific IgE levels and pollinosis, suggesting that -1590C/T may have more impact on sensitization and disease development than R668Q. Our results suggest that the MMP9 gene confers susceptibility to cedar pollinosis in Japanese children. The MMP9 gene may be associated with pollinosis through sensitization processes.

Effects of aging on the natural history of seasonal allergic rhinitis in middle-aged subjects in South chiba, Japan.

BACKGROUND: The natural history of allergic rhinitis has been examined in a few longitudinal studies. The purpose of the study was to investigate the course, development and remission of seasonal allergic rhinitis (SAR) over 10 successive years in middle-aged subjects. METHODS: An annual questionnaire survey on allergic rhinitis symptoms combined with an examination of specific IgE has been undertaken in a rural town in south Chiba since 1995. The analyzed subjects were 703 residents who underwent every examination in 1995, 2004 and 2005. In the last 15 years, the annual pollen count in Chiba was highest in 2005. RESULTS: The sensitization rates to cedar pollen decreased with age in the same subject groups over 10 years, but the prevalence of SAR was higher in 2005 compared with 1995. Of the 52 subjects with SAR in 1995, the symptoms had disappeared in 10 subjects in 2005. Specific IgE had converted to negative or borderline in 4 of these patients, had decreased but was still positive in 4 and was increased or unchanged in 2. During the 10-year period, 22 subjects developed SAR, of whom 12 had increased specific IgE and 10 had similar or decreased specific IgE in 2005. CONCLUSION: SAR induced by cedar pollen takes a chronic course in the majority of middle-aged patients in south Chiba, Japan. The prevalence of SAR increased over 10 years due to a high level of pollen exposure. Changes in specific IgE were not directly associated with the development or remission of SAR.

Comparison of nasal steroid with antihistamine in prophylactic treatment against pollinosis using an environmental challenge chamber.

Environmental challenge chambers (ECC) have been used to expose people to pollen allergens within a stable atmosphere and to examine the efficacy of treatment. Although pollinosis is one of the typical IgE-mediated type I allergic diseases, allergic inflammation is thought to contribute to the fundamental pathogenesis and prophylactic treatment may reduce exacerbations of pollinosis. The purpose of this study was to compare the efficacy of prophylactic treatment with nasal steroid (mometasone furoate nasal spray) or an antihistamine (fexofenadine) in the control of cedar pollinosis using the ECC. In a randomized, double-blind two-way crossover study, 48 patients received nasal steroid or antihistamine for 7 consecutive days (days 1-7). On day 8, patients were exposed to cedar pollen (8000 grains/m(3)) in the ECC for 3 hours. Nasal symptoms induced by pollen exposure were assessed. Total nasal symptom scores (TNSSs) during the exposure in the ECC were not significantly different between the antihistamine and the nasal steroid groups. Nasal symptoms induced by pollen exposure using the ECC persisted for up to 3 days. TNSSs after pollen exposure on days 8-11 were significantly lower in the nasal steroid group compared with the antihistamine group. Prophylactic treatment with nasal steroid is more effective than antihistamine against pollinosis, particularly in the late phase. Clinical trial registration JAPIC CTI 101182 (www.clinicaltrials.jp/user/ctiMain_e.jsp).

Induction of NKT cell-specific immune responses in cancer tissues after NKT cell-targeted adoptive immunotherapy.

Vα24 natural killer T (NKT) cells have potent anti-tumor activity. We performed a phase II clinical study in patients with head and neck squamous cell carcinoma (HNSCC) using ex vivo expanded Vα24 NKT cells and α-galactosylceramide (αGalCer; KRN7000)-pulsed antigen-presenting cells (APCs) to investigate the efficacy and induction of NKT cell-specific immune responses. The subjects were 10 patients with locally recurrent and operable HNSCC. One course of nasal submucosal administration of αGalCer-pulsed APCs and intra-arterial infusion of activated NKT cells via tumor-feeding arteries was given before salvage surgery. Anti-tumor effects, NKT cell-specific immune responses in extirpated cancer tissue and peripheral blood, safety, and pathological effects were evaluated. Five cases achieved objective tumor regression. The number of NKT cells increased in cancer tissues in 7 cases and was associated with tumor regression. The combination therapy induced NKT cell-specific immune responses in cancer tissues that were associated with beneficial clinical effects.

Increase of regulatory T cells and the ratio of specific IgE to total IgE are candidates for response monitoring or prognostic biomarkers in 2-year sublingual immunotherapy (SLIT) for Japanese cedar pollinosis.

The aims of this study were to examine the therapeutic effects of sublingual immunotherapy (SLIT) and to identify potential biomarkers that would predict the therapeutic response in a randomized, double-blind, placebo-controlled clinical trial. The trial was carried out over two pollinosis seasons in 2007 and 2008. Carry-over therapeutic effects were analyzed in 2009. SLIT significantly ameliorated the symptoms of pollinosis during the 2008 and 2009 pollen seasons. Cry j 1-specific cytokine production in a subgroup of patients with mild disease in the SLIT group was significantly attenuated. The ratio of specific IgE to total IgE before treatment correlated with the symptom-medication score in the SLIT group in 2008. Patients with increased Cry j 1-iTreg in the SLIT group had significantly improved QOL and QOL-symptom scores. In summary, the specific IgE to total IgE ratio and upregulation of Cry j 1-iTreg are candidates for biomarker of the clinical response to SLIT.

Migration and immunological reaction after the administration of αGalCer-pulsed antigen-presenting cells into the submucosa of patients with head and neck cancer.

BACKGROUND: Antigen-presenting cells (APCs) play a crucial role in the induction of immune responses. However, the optimal administration route of tumor-specific APCs for inducing effective immunological responses via cancer immunotherapy remains to be elucidated. Human NKT cells are known to have strong anti-tumor activities and are activated by the specific ligand, namely, α-galactosylceramide (αGalCer). METHODS: Seventeen patients with head and neck squamous cell carcinoma (HNSCC) were enrolled in this study. Patients received an injection of αGalCer-pulsed APCs into the nasal, or the oral floor submucosa. Then total body image and single photon emission computed tomography (SPECT) images were examined. The immunological responses including the number of peripheral blood NKT cells, anti-tumor activities and the CD4(+) CD25(high) Foxp3(+) T cells (Tregs) induced following APCs were also compared. RESULTS: APCs injected into the nasal submucosa quickly migrated to the lateral lymph nodes and those injected into the oral floor submucosa dominantly migrated to the submandibular nodes rather than the lateral lymph nodes. An increase in the absolute number of NKT cells and the IFN-γ producing cells was observed in peripheral blood after injection of the APCs into the nasal submucosa, however, these anti-tumor activities were not detected and the increased frequency of Treg cells were observed after administration into oral floor. CONCLUSIONS: These results indicate that a different administration route of APCs has the potential to bring a different immunological reaction. The submucosal administration of αGalCer into the oral submucosa tends to induce immunological suppression.

The influence of environmental exposure to formaldehyde in nasal mucosa of medical students during cadaver dissection.

BACKGROUND: Environmental exposure to formaldehyde is commonly associated with clinical symptoms such as mucosal irritation and olfactory disorders. However, the impact of such exposure on the development of mucosal inflammation and its outcome has not been carefully evaluated. METHODS: The observational non-comparative study was planned. The study population consisted of group of 41 medical students who had signed up for a cadaver dissection course as part of their gross anatomy teaching at the school of medicine Chiba University in Japan. During such dissection course, the students are exposed to variable levels of environmental formaldehyde routinely employed for the preservation the cadavers. The subjects were evaluated by a detailed medical examination. We measured their serum IgE levels. In addition, an olfaction test and nasal mucosal sensitivity to histamine was serially determined, immediately before and after the course and 6 months after the completion of the course. RESULTS: Olfactory abnormalities were observed in 13/41 (32%) subjects and increased nasal mucosal hypersensitivity to histamine was observed in 17/41 (41%) during and immediately after completion of the course. These subjects had evidence of preexisting allergic rhinitis. 6/41 (15%) other students with no prior evidence of allergic rhinitis also exhibited formaldehyde associated clinical symptoms during the dissecting course. However, the symptoms disappeared upon completion of the course in all subjects studied. CONCLUSIONS: Temporary abnormalities in the olfaction test and increased nasal mucosal hypersensitivity to histamine were observed in a few students with preexisting allergic rhinitis after environmental exposure of high concentrations of formaldehyde. These effects appeared to be transient.

The effect of radiotherapy on NKT cells in patients with advanced head and neck cancer.

BACKGROUND: Cancer immunotherapy with NKT cells is a potential new treatment strategy for advanced head and neck cancer. NKT cell therapy is promising due to its unique anti-tumor activity and higher degree of safety compared to current therapies. Radiotherapy is indispensable as a standard treatment for advanced head and neck cancer. To elucidate the possibility of using NKT cells as an adjuvant immunotherapy with radiotherapy, we examined the effect of radiotherapy on NKT cells in patients with head and neck cancer. METHODS: The number, IFN-gamma production and proliferation capacity of NKT cells were analyzed before and after 50 Gy radiation therapy in 12 patients with stage IV head and neck squamous cell carcinoma. The cytotoxic activity of NKT cells was examined in vitro. RESULTS: The number of NKT cells in the blood varied widely between patients. After radiation therapy, the population of CD3 T cells decreased significantly, while the NKT cell population remained stable. The number of NKT cells was the same after radiation therapy as before. IFN-gamma production from NKT cells collected just after radiotherapy was impaired after stimulation with exogenous ligand, but the proliferative responses of these NKT cells was enhanced in comparison to those collected before radiation therapy. Furthermore, the proliferated NKT cells displayed a significant level of anti-tumor activity. CONCLUSION: NKT cells are relatively resistant to radiation and might therefore be suitable for adjuvant immunotherapy to eradicate remnant cancer cells in patients who have undergone radiation therapy.

The induced regulatory T cell level, defined as the proportion of IL-10(+)Foxp3(+) cells among CD25(+)CD4(+) leukocytes, is a potential therapeutic biomarker for sublingual immunotherapy: a preliminary report.

BACKGROUND: Japanese cedar (Cryptomeria japonica) pollinosis is one of the most prevalent allergies in Japan. Recently, two reports described the positive effects of sublingual immunotherapy (SLIT) against Japanese cedar pollinosis. However, the therapeutic biomarkers for SLIT are still unclear. We performed this unblinded, nonrandomized, open-label study to identify therapeutic biomarkers for SLIT against Japanese cedar pollinosis. METHODS: We performed an open-label study during one pollinosis season in 2007, enrolling 19 patients from in-house volunteers suffering from Japanese cedar pollinosis. Peripheral blood was obtained from all participants before SLIT treatment as well as before and after the pollen season. The plasma levels of an immunoglobulin specific to a major allergen (Cry j 1) were determined. We analyzed the induction of regulatory T cells (iTregs), namely IL-10(+)Foxp3(+) cells in CD25(+)CD4(+) leukocytes, by flow cytometry. The Th2-type responses were analyzed by cytokine production from peripheral blood mononuclear cells after stimulation with Cry j 1. Clinical symptoms were estimated using a quality of life questionnaire in the middle of the pollen season. RESULTS: The difference in numbers of iTregs between the medium-only control cell culture and cells stimulat- ed with Cry j 1 was significantly decreased in the non-SLIT group but was unchanged in the SLIT group after the pollen season. The subgroup of the SLIT group with increased iTregs showed more attenuated Th2-type cytokine profiles, and symptom scores in the subgroup with increased iTregs were significantly lower than those in the subgroup with decreased iTregs. CONCLUSION: The antigen-specific iTreg level is a potential therapeutic biomarker that correlates with clinical pollinosis symptoms and may be involved in the therapeutic mechanisms of SLIT.

Reevaluation of pollen quantitation by an automatic pollen counter.

Accurate and detailed pollen monitoring is useful for selection of medication and for allergen avoidance in patients with allergic rhinitis. Burkard and Durham pollen samplers are commonly used, but are labor and time intensive. In contrast, automatic pollen counters allow simple real-time pollen counting; however, these instruments have difficulty in distinguishing pollen from small nonpollen airborne particles. Misidentification and underestimation rates for an automatic pollen counter were examined to improve the accuracy of the pollen count. The characteristics of the automatic pollen counter were determined in a chamber study with exposure to cedar pollens or soil grains. The cedar pollen counts were monitored in 2006 and 2007, and compared with those from a Durham sampler. The pollen counts from the automatic counter showed a good correlation (r > 0.7) with those from the Durham sampler when pollen dispersal was high, but a poor correlation (r < 0.5) when pollen dispersal was low. The new correction method, which took into account the misidentification and underestimation, improved this correlation to r > 0.7 during the pollen season. The accuracy of automatic pollen counting can be improved using a correction to include rates of underestimation and misidentification in a particular geographical area.

Sublingual immunotherapy with house dust extract for house dust-mite allergic rhinitis in children.

BACKGROUND: House dust extract is used in conventional immunotherapy for house dust-mite (HDM) allergic rhinitis in Japan. However, an alternative administration route is desired. The aims of the present double blind, placebo-controlled trial were to evaluate the therapeutic efficacy and safety of sublingual immunotherapy (SLIT) with house dust extract in pediatric patients with HDM allergic rhinitis. METHODS: The study population comprised 31 subjects (21 males and 10 females) aged from 7 to 15 years old. Twenty patients (the active group) received house dust extract and 11 received placebo via sublingual administration. Extract or placebo (1 ml) was administered at 10-fold dilution once weekly for 40 weeks. During the study period, the subjects recorded their daily nasal symptoms and use (dose and frequency) of other medications in a nasal allergy diary. RESULTS: The symptom scores in the active group began to decrease about 24 weeks after initiation of treatment and significant differences between the active and placebo groups were observed after 30 weeks. The average scores for the last four weeks of the study were significantly lower than those for the first four weeks in the active group but not in the placebo group. The only local adverse effect was a bitter taste reported by one patient. There were no other local or systemic adverse effects associated with SLIT. CONCLUSIONS: Our results suggest that SLIT with house dust extract for more than 30 weeks is safe and effective treatment for HDM allergic rhinitis in children.

Combination therapy of in vitro-expanded natural killer T cells and alpha-galactosylceramide-pulsed antigen-presenting cells in patients with recurrent head and neck carcinoma.

The aim of this clinical trial was to investigate the feasibility of intra-arterial infusion of in vitro-expanded Valpha24 natural killer T (NKT) cells combined with submucosal injection of alpha-galactosylceramide (KRN7000; alphaGalCer)-pulsed antigen-presenting cells (APC). A phase I clinical study was carried out in patients with head and neck squamous cell carcinoma (HNSCC). Patients with locally recurrent HNSCC refractory to standard therapy were eligible. Eight patients received super-selective transcatheter intra-arterial infusion of activated Valpha24 NKT cells into tumor-feeding arteries and nasal submucosal injections of alphaGalCer-pulsed APC twice with a 1-week interval. Valpha24 NKT cell-specific immune responses, safety, and antitumor effects were evaluated. The number of Valpha24 NKT cells and interferon-gamma-producing cells in peripheral blood mononuclear cells increased in seven out of eight patients enrolled. Grade 3 toxicity with a pharyngocutaneous fistula related to local tumor reduction was observed in one patient and mild adverse events with grade 1-2 symptoms occurred in seven patients. Regarding the clinical responses, three cases exhibited a partial but significant response, four were classified as stable disease, and one patient continued to develop progressive disease. The use of the intra-arterial infusion of activated Valpha24 NKT cells and the submucosal injection of alphaGalCer-pulsed APC has been shown to induce significant antitumor immunity and had beneficial clinical effects in the management of advanced HNSCC. The use of such therapeutic modalities may be helpful in the management of tumors and therefore needs to be explored in further detail. The clinical trial registration number was UMIN000000722.

Cedar and cypress pollinosis and allergic rhinitis: quality of life effects of early intervention with leukotriene receptor antagonists.

BACKGROUND: Allergic rhinitis involves inflammation of the nasal passages. The use of nasal steroids is generally very effective in providing significant symptom relief. However, compliance for their use is sometimes poor. METHODS: To examine the efficacy of early intervention (before pollen dispersal) with oral cysteinyl leukotriene receptor antagonists (LTRA) on pollinosis in patients with allergy to cedar and Japanese cypress pollens, groups of subjects were treated with LTRA or a placebo for 4 weeks at the beginning of the cedar pollen dispersal season. Subsequently, all patients received nasal steroid therapy concomitantly with LTRA throughout the remaining period of the pollen dispersal season. The effects of such early treatment with LTRA on pollinosis were investigated using symptom scores from an allergy diary and quality of life (QOL) scores. RESULTS: Sneezing and nasal congestion scores were significantly lower in the LTRA-pretreated subjects than observed in the placebo-pretreated patients between weeks 4 and 6 and weeks 3 and 5, respectively. QOL scores improved significantly in all domains after concomitant therapy with nasal steroids. The percent improvement in the nasal congestion score after the concomitant therapy was significantly higher in the LTRA group (69%) than in the placebo group (41%). CONCLUSION: Significant differences observed in symptoms and in QOL effects between LTRA- and placebo-pretreated patients and the absence of major adverse effects noted in these studies suggest that early intervention with LTRA is beneficial and safe and should be considered in the management of pollinosis-associated allergic rhinitis.

Effects of daily intake of Lactobacillus paracasei strain KW3110 on Japanese cedar pollinosis.

Japanese cedar pollinosis is an important contributor to allergic rhinitis in Japan. Lactobacillus may be useful as an immunomodulator and is used widely as a foodstuff. The purpose of the study was to examine the effects of daily intake of the Lactobacillus paracasei strain KW3110 in patients with cedar pollinosis. The effects of daily intake of KW3110 in patients with cedar pollinosis were investigated in 126 patients who received KW3110 or a placebo in a double-blind study. The study began 1 month before the start of the pollen season and lasted for 3 months. A significant reduction of nasal symptoms and the serum level of eosinophil cationic protein and improvement of quality of life scores occurred in the patients who received KW3110 when pollen scattering was low. However, the effects were limited during the peak period of pollen scattering. Intake of KW3110 may reduce allergic inflammation, but the effect is limited.

Present situation of cedar pollinosis in Japan and its immune responses.

Recent observations have suggested significant worldwide increase in the prevalence of allergic rhinitis and cedar pollinosis. In Japan, Japanese cedar (Cryptometria japonica) and Japanese cypress (Chamaecyparis obtusa) pollens are considered to be the major unique allergens and their extent of dispersal is quite large, travelling more than 100km and thus causing serious pollinosis. Cedar pollinosis is a typical type 1 allergic disease by an adaptive immune response that occurs through the induction of allergen-specific effector T cells from naïve T cells. We examined the number of Japanese cedar pollen specific memory Th cells in the peripheral blood of the patients and found that the cedar pollen specific IL-4-producing Th2 memory cells increased during the pollen season and decreased during the off-season. However, more than 60% of the cedar-specific memory Th2 cells survived up to 8 months after the pollen season. Natural killer T(NKT) cells represent a unique lymphocyte subpopulation and their activity is not restricted to MHC antigens. NKT cells play an important role in innate immunity, however, the participation in development of allergic rhinitis could not be clarified.

A randomized controlled trial of sublingual immunotherapy for Japanese cedar pollinosis.

BACKGROUND: Japanese cedar pollen represents an important and unique allergen. Sublingual immunotherapy (SLIT) has been suggested to be a highly effective route of desensitization against a variety of allergens. However, little information is available about its use in cedar pollen allergy. METHODS: A blinded randomized, placebo-controlled trial employing SLIT for cedar pollinosis was conducted over a period of 6 months. Sixty-seven subjects were enrolled and the symptom scores during the pollen season were evaluated by a symptom diary, measurement of cedar-specific IgE and IgG4, and determination of Cry j-specific Th2 clones before SLIT and before and after the pollen season. RESULTS: No major adverse effects were observed in either group. The serum-specific IgG4 activity increased significantly after SLIT in the active group. The active group also exhibited significantly lower symptom scores compared to the placebo. The specific Th2 clone sizes were not significantly different between the groups before the pollen season. However, an increase in the clone size was observed after the pollen season in the placebo group, but not in the active group. CONCLUSION: Use of SLIT for Japanese cedar pollinosis was found to be safe and associated with an increase in cedar-specific IgG4 levels. Such therapy inhibited the increase in Cry j-specific Th2 clone size induced by pollen exposure. Finally, use of SLIT resulted in significant improvement of the clinical symptoms of cedar pollinosis in this patient population. These observations suggest that SLIT may offer another safe approach to the management of cedar pollinosis.