Geissoschizine methyl ether, an alkaloid in Uncaria hook, is a potent serotonin 1A receptor agonist and candidate for amelioration of aggressiveness and sociality by yokukansan.

Yokukansan (YKS), a traditional Japanese medicine, is composed of seven kinds of dried herbs. It is widely prescribed in clinical situation for treating psychiatric disorders such as aggressiveness in patients with dementia. We previously demonstrated that YKS and Uncaria hook (UH), which is a constituent herb of YKS, had a partial agonistic effect to 5-HT(1A) receptors in vitro. However, it has still been unclear whether this in vitro effect is reflected in in vivo, and what the active ingredients are. The purpose of the present study is to find the active ingredient in YKS and to demonstrate the effect in in vivo. In the present study, we first studied the effect of YKS and UH on aggressiveness and sociality in socially isolated mice. YKS and UH ameliorated the isolation-induced increased aggressiveness and decreased sociality, and these ameliorative effects were counteracted by coadministration of 5-HT(1A) receptor antagonist WAY-100635, or disappeared by eliminating UH from YKS. These results suggest that the effect of YKS is mainly attributed to UH, and the active ingredient is contained in UH. To find the candidate ingredients, we examined competitive binding assay and [(35)S] guanosine 5'-O-(3-thiotriphosphate) (GTPγS) binding assay of seven major alkaloids in UH using Chinese hamster ovary cells expressing 5-HT(1A) receptors artificially. Only geissoschizine methyl ether (GM) among seven alkaloids potently bound to 5-HT(1A) receptors and acted as a partial agonist. This in vitro result on GM was further demonstrated in the socially isolated mice. As did YKS and UH, GM ameliorated the isolation-induced increased aggressiveness and decreased sociality, and the effect was counteracted by coadministration of WAY-100635. These lines of results suggest that GM in UH is potent 5-HT(1A) receptor agonist and a candidate for pharmacological effect of YKS on aggressiveness and sociality in socially isolated mice.

High temporal and spatial quality petawatt-class Ti:sapphire chirped-pulse amplification laser system.

Optical parametric chirped-pulse amplification (OPCPA) operation with low gain by seeding with high-energy, clean pulses is shown to significantly improve the contrast to better than 10(-10) to 10(-11) in a high-intensity Ti:sapphire laser system that is based on chirped-pulse amplification. In addition to the high-contrast broadband, high-energy output from the final amplifier is achieved with a flat-topped spatial profile of filling factor near 77%. This is the result of pump beam spatial profile homogenization with diffractive optical elements. Final pulse energies exceed 30 J, indicating capability for reaching peak powers in excess of 500 TW.

The herbal medicine Toki-shakuyaku-san improves the hypertension and intrauterine growth retardation in preeclampsia rats induced by Nomega-nitro-L-arginine methyl ester.

The chronic inhibition of nitric oxide (NO) synthesis with Nomega-nitro-L-arginine methyl ester (L-NAME) induces a preeclampsia-like syndrome including hypertension and intrauterine growth retardation (IUGR) in pregnant rats. We tested the traditional herbal medicine Toki-shakuyaku-san (TS) for beneficial effects in this model. L-NAME was infused subcutaneously into pregnant rats from day 14 of gestation. TS (1 g/kg, 2 g/kg) was administered by gavage from day 14 to 20. Systolic blood pressure was measured on day 19. On day 20, rats were sacrificed and serum NO levels, placental weight, fetal body weight, fetal cerebrum weight and the thickness of the cerebral cortex were analyzed. TS (1 g/kg, 2 g/kg) inhibited L-NAME-induced hypertension. The decrease in fetal body weight, cerebrum weight and thickness of the cerebral cortex was abrogated by TS (2 g/kg). The effect of TS on blood pressure was found only in the rats that were both pregnant and infused with L-NAME. L-arginine, at the amount equivalent to that contained in TS, showed no effect. Further, the change in serum NO levels induced by TS was only marginal. TS thus improved the hypertension and IUGR in preeclampsia rats induced by L-NAME in a NO-independent manner. These data suggested that TS may be beneficial for the treatment and prevention of preeclampsia.

Effects of the extract of the bark of Magnolia obovata and its biphenolic constituents magnolol and honokiol on histamine release from peritoneal mast cells in rats.

We have previously reported that saiboku-to, an Oriental herbal remedy composed of a mixture of 10 different herbal extracts, possesses anti-histamine release effect on mast cells in rats. This effect may be due mainly to the extract of the bark of Magnolia obovata (M. obovata), a constituent herb of saiboku-to. In the present study, it was demonstrated that the bark extract inhibited compound 48/80 (C48/80)-induced histamine release from mast cells in a concentration-dependent manner (50 % inhibitory concentration, IC(50) = 56.98 microg/ml). Furthermore, the inhibitory activity was found in the methanol fraction, but not in water and 50 % aqueous methanol fractions derived from the bark extract. Magnolol and honokiol isolated from the methanol fraction inhibited C48/80-induced histamine release from mast cells. The potency of magnolol (IC(50) = 1.04 microg/ml) was greater than that of honokiol (IC(50) = 2.77 microg/ml). Furthermore, the actual amount of magnolol (49.76 +/- 1.14 mg) contained in the bark of M. obovata (5 g) was greater than that (8.58 +/- 0.19 mg) of honokiol. Taken together, the present results suggest that magnolol may be responsible for the biological efficacy of the bark extract of M. obovata.

[The role of psychosomatic medicine in public health (hygieiology): an approach for lifestyle-related disease].

In the twenty-first century it has been hypothesized that lifestyle-related disease will account for more than 70% of all disease; thus, in the twenty-first the prevention and treatment of lifestyle-related disease will be of primary importance. Lifestyle differs from individual to individual. In the past preventive medicine has targeted groups while clinical medicine has dealt with disease. However, in the twenty-first century it will be necessary to integrate the two approaches to meet the needs of the individuals. Measures following the primary prevention of lifestyle-related disease will be the vital and they can only be delivered by primary care medicine. As a model that covers the prevention and treatment of lifestyle-related diseases, based on the conventional biomedical model, a systematic medical model that attaches importance to the relativity of all factors and individuality will be necessary. The medical model for psychosomatic medicine is the Bio-psycho-socio-ethical (ecological) model, and psychosomatic medicine has specific methods for implementing this model. We have used this perspective to explain the role of psychosomatic medicine in public health (hygieiology).

Allergen-induced mRNA expression of IL-5, but not of IL-4 and IFN-gamma, in peripheral blood mononuclear cells is a key feature of clinical manifestation of seasonal allergic rhinitis.

OBJECTIVES: To investigate the allergen-induced messenger RNA (mRNA) expression of interleukin (IL) 4, IL-5 and interferon gamma (IFN-gamma) in peripheral blood mononuclear cells from individuals sensitized by Japanese cedar (Cryptomeria japonica) pollens, and to elucidate the clinical role of IL-4, IL-5, and IFN-gamma in the allergen sensitization and clinical manifestation of allergic disorders. DESIGN: This study included 30 patients sensitized to the pollen and 14 nonatopic healthy volunteers. Peripheral blood mononuclear cells (1.0 x 10(6) cells/mL) of each individual were cultured at 37 degrees C for 24 hours in the presence of 10 microg/mL of Cry j 1, a major allergen of the pollens. Total cellular RNA was extracted from the peripheral blood mononuclear cells, and IL-4, IL-5, and IFN-gamma mRNA expression was determined with a reverse transcriptase polymerase chain reaction. RESULTS: From the results of a survey of symptom diary cards and interviews regarding nasal symptoms during the pollen season in 1998, we found that 20 patients (symptomatic group), but not 10 patients (asymptomatic group), had typical symptoms of seasonal allergic rhinitis. Interleukin 4 mRNA was not expressed in the nonatopic subjects but was expressed in 9 asymptomatic patients and in 17 symptomatic patients. Interleukin 5 mRNA was exclusively expressed in the symptomatic patients. Interferon gamma mRNA expression did not differ significantly among the nonatopic subjects, asymptomatic patients, and symptomatic patients. CONCLUSIONS: This study has clearly highlighted an interesting and new concept that IL-4 is implicated in allergen sensitization but not in clinical manifestation, and that IL-5 may not be a feature of atopy in itself but seems to be a hallmark of clinical manifestation of ongoing atopic diseases.

Modulation of lung local immune responses by oral administration of a herbal medicine Sho-saiko-to.

Sho-saiko-to (SST), a Chinese/Japanese herbal medicine (Kampo medicine) widely used to treat chronic hepatitis in Japan, is known to modulate immune responses, and thus its immunomodulating activity may be responsible for its bi-directional effects on the lungs as therapeutic efficacy in various lung diseases and involvement in development of interstitial pneumonia. We administered SST to BALB/c mice orally and examined the lung tissue levels of pro/anti-inflammatory cytokines, interleukin-1beta (IL-1beta), tumor necrosis factor-alpha (TNF-alpha) and interleukin-6 (IL-6), and the effects of SST on acute lung injury induced by instillation of lipopolysaccharide (LPS) or IL-1. Although SST had no effect on lung TNF-alpha or IL-1beta level, it increased IL-6. Investigation of active fractions of SST suggested that multiple ingredients were supposed to be responsible for IL-6-inducing activity. Liquiritigenin, a metabolite of liquiritin which is one of the major ingredients in SST enhanced in vitro IL-6 production in anti-CD3 monoclonal antibody (anti-CD3 mAb)-stimulated lung mononuclear cells in a cell-type specific and dose-dependent manner. SST suppressed LPS-induced lung injury at the later phase when lung leak was evident while being ineffective on initial neutrophil sequestration to the lung in these models. These findings suggest that SST modulates lung inflammation by regulating local immune response.

Allergen induced mRNA expression of interleukin-5, but not of interleukin-4 and interferon-gamma, in peripheral blood mononuclear cells obtained before the pollen season predicts the clinical efficacy of immunotherapy for seasonal allergic rhinitis.

The primary aim of this study was to investigate whether the allergen-induced synthesis of cytokines by peripheral blood mononuclear cells (PBMCs) obtained immediately before the pollen season could predict the clinical efficacy of immunotherapy during the following pollen season. PBMCs (1.0 x 106 cells/ml) were obtained from 17 nonatopic subjects and from 60 patients receiving immunotherapy for seasonal allergic rhinitis (caused by Japanese cedar pollens) immediately before the pollen season of 1998, and were cultured for 24 h in the presence of 10 mg/ml of Cry j 1, a major allergen of Japanese cedar pollens, at 37 degrees C in a fully humidified 5% CO2 atmosphere. Total cellular RNA was extracted from the PBMCs, and the allergen-induced interleukin (IL)-4, IL-5 and interferon-gamma (IFN-gamma) mRNA expression was determined using a reverse transcription-polymerase chain reaction. According to the nasal symptoms during the pollen season of 1998, the 60 patients on immunotherapy were divided into 36 good responders (who had no nasal symptoms and no requirement for rescue medications) and 24 poor responders who needed rescue medications to control nasal symptoms. Neither IL-4 mRNA nor IL-5 mRNA was expressed in any of the 17 nonatopic individuals. By contrast, IL-4 mRNA was expressed in 26 good responders and in 22 poor responders, and IL-5 mRNA was expressed in eight good responders (22.2%) and in 23 poor responders (95.8%). IFN-gamma mRNA was expressed in four nonatopic subjects, in nine good responders and in seven poor responders. The expression of IFN-gamma did not differ significantly among the nonatopic subjects, the good responders and the poor responders. The mRNA expression of IL-5 (P < 0.0001), but not of IL-4 (P = 0.0999) and IFN-gamma (P = 0. 7713), differed significantly between the good and poor responders. Therefore, our study has highlighted that positive expression of IL-5 mRNA in PBMCs sampled immediately before the pollen season could be predictive of a poor clinical outcome of immunotherapy during the following pollen season and that the down-regulation of IL-5 mRNA expression in PBMCs could be an important mechanism of pollen immunotherapy related to the clinical efficacy.

Pollen immunotherapy inhibits T helper 1 and 2 cell responses, but suppression of T helper 2 cell response is a more important mechanism related to the clinical efficacy.

OBJECTIVES: To investigate the allergen-induced IgE synthesis and cytokine production by peripheral blood mononuclear cells from patients with seasonal allergic rhinitis due to Japanese cedar (Cryptomeria japonica) pollens and to elucidate the immunological mechanisms related to the clinical efficacy of immunotherapy (IT) for seasonal allergic rhinitis. DESIGN: This study included 51 patients with seasonal allergic rhinitis due to the pollen and 8 nonatopic healthy volunteers (nonatopic group). Thirty-nine patients had been undergoing IT using the pollen extracts for various lengths of time (IT group). The remaining 12 patients had never been treated with IT (untreated group). Peripheral blood mononuclear cells (3.3 x 10(6) cells per milliliter) from each individual were cultured with Cry j 1, 4.17 microg/mL. After 96 hours, culture supernatants were harvested to determine the concentrations of IgE, interleukin (IL) 5, interferon gamma (IFN-gamma), and tumor necrosis factor alpha (TNF-alpha). RESULTS: The levels of IgE (P = .02), IL-5 (P<.01), and TNF-alpha (P = .05) were significantly higher in the untreated group than in the nonatopic group. The levels of IFN-gamma did not differ significantly between the untreated and the nonatopic groups (P = .19). The levels of IgE, IL-5, and IFN-gamma, but not of TNF-alpha, were inversely correlated with the duration (in years) of IT, and none of the levels of IgE (P = .74), IL-5 (P = .15), IFN-gamma (P = .61), and TNF-alpha (P = .55) differed significantly between the nonatopic group and those who had been treated with IT for 10 years or more. The levels of IL-5 were significantly lower in the good responders than in the poor responders to IT (P<.001), whereas the levels of total IgE (P = .20), IFN-gamma (P = .16), and TNF-alpha (P = .14) did not differ significantly between them. CONCLUSION: The mechanisms responsible for the clinical efficacy of pollen IT are principally related to the tolerance or anergy of T helper 2 cells.

Effectiveness of local anesthesia in pediatric dental practice.

BACKGROUND: Pain control in dental treatment for children is very important. The purpose of this study is to describe the characteristics of local anesthetic use by pediatric dentists and to examine factors related to its effectiveness in children. METHODS: The authors observed 361 patients in 17 pediatric dental practices in Washington state while each child received restorative or surgical dental treatment. The authors recorded data concerning local anesthetic use and effectiveness. The children's mean age was 87 months, and 181 (50.1 percent) of the patients were girls. A pediatric dentist observer rated each child's anxiety before the initial injection of local anesthetic and the effectiveness of pain control during restorative treatment. The observing dentist asked the treating dentist about the effectiveness of pain control after completion of treatment. RESULTS: Forty-two of 361 children (11.6 percent) were observed to experience ineffective pain control. Fourteen of 17 dentists (82.4 percent) were observed to have at least one patient in whom pain control was ineffective. Lidocaine (2 percent with 1:100,000 epinephrine) was used by 15 of 17 dentists (88.2 percent) and in 312 of 361 cases (86.4 percent). The average amount of agent was one cartridge (36 milligrams of lidocaine). Children who were anxious, who had symptoms before treatment, and who underwent more invasive operative and endodontic procedures were more likely to experience ineffective pain control. CONCLUSIONS: The data suggest that painful treatment is relatively frequent even in specialized pediatric practice. Variability in general practice is likely to be greater. CLINICAL IMPLICATIONS: The incidence of ineffective pain control may be less if clinicians use methods to reduce anxiety and perioperative infection and symptoms.

The effect of leptin on feeding-regulating neurons in the rat hypothalamus.

Intense immunoreactivity for the leptin receptor was detected in the hypothalamic arcuate nucleus (ARC), ventromedial nucleus (VMH), and lateral hypothalamus (LH) by immunohistochemistry. Cytosolic Ca2+ concentration ([Ca2+]i) in single neurons isolated from the ARC, VMH and LH was measured with dual wavelength fura-2 fluorescence imaging. A reduction of the superfusate glucose concentration from 10 to 1 mM increased [Ca2+]i in 21% of ARC neurons and 22% of LH neurons. Leptin at 0.1 nM inhibited the [Ca2+]i increase in 66 and 64% of these glucose-sensitive ARC and LH neurons, respectively. Inversely, 10 mM glucose increased [Ca2+]i in 49% of the VMH neurons, and 0.1 nM leptin at 1 mM glucose also increased [Ca2+]i in 84% of these glucose-responsive neurons. These results reveal that leptin inhibits the ARC and LH neurons and stimulates the VMH neurons via the leptin receptor expressed in these cells.

Molecular cloning and characterization of a novel developmentally regulated gene, Bdm1, showing predominant expression in postnatal rat brain.

Postnatal development, such as synapse refinement, is necessary for the establishment of a mature and functional central nervous system (CNS). Using differential display analysis, we identified a novel gene, termed Bdm1, that is more abundantly expressed in the adult brain than in the embryonic brain. The full-length Bdm1 cDNA is 2718 base pairs long and contains an open reading frame of 1059 base pairs encoding a 38-kDa protein. Northern blot analysis revealed that expression of Bdm1 mRNA in the brain was weak on embryonic days and increased in the early postnatal period. Bdm1 mRNA was significantly expressed in the brain and heart, but there was no or little expression in other tissues. During the differentiation of mouse carcinoma cells P19 to neuron-like cells by retinoic acid, Bdm1 mRNA was up-regulated almost parallel to neurofilament mRNA. Expression of Bdm1 mRNA was observed appreciably in PC12 cells after neuronal differentiation but not in the nonneural cell lines examined. In situ hybridization demonstrated that Bdm1 was expressed widely in the olfactory bulb, cerebral cortex, hippocampus, cerebellum, thalamus, and medulla oblongata. Taken together, these data suggest that Bdm1 gene plays a role in the early postnatal development and function of neuronal cells.

Specific immunoglobulin E, interleukin-4, and soluble vascular cell adhesion molecule-1 in sera in patients with seasonal allergic rhinitis.

This study included 23 nonatopic volunteers and 84 patients with seasonal allergic rhinitis due to Japanese cedar pollen. Serum interleukin-4 (IL-4) and soluble vascular cell adhesion molecule-1 (sVCAM-1) in the patients were significantly higher than those in the nonatopic individuals, even outside of the pollen season. Both the good responders and the poor responders to antihistamine tablets showed significant increases in IL-4 and specific IgE during the pollen season, whereas such seasonal increases were not observed in the good responders to immunotherapy. Seasonal increases in IL-4 were significantly correlated with those of specific IgE. However, seasonal increases in sVCAM-1 were not significant. Seasonal increases in sVCAM-1 were not significantly different between the good responders and the poor responders to pharmacotherapy or immunotherapy. In conclusion, serum IL-4 and sVCAM-1 are increased in patients with seasonal allergic rhinitis, even outside of the pollen season; this finding might suggest underlying preponderant in vivo activation of T helper cell-2-like cells and inflammatory events in seasonal allergic rhinitis. A seasonal increase in IL-4 in sera might be at least partly involved in the seasonal increase in specific IgE in sera. Immunotherapy's inhibitory effect on IL-4 production and specific IgE response might be one of its working mechanisms.

Effects of Sho-saiko-to, a Japanese herbal medicine, on hepatic fibrosis in rats.

It has been shown that lipid peroxidation is associated with hepatic fibrosis and stellate cell activation. Sho-saiko-to (TJ-9) is an herbal medicine, which is commonly used to treat chronic hepatitis in Japan, although the mechanism by which TJ-9 protects against hepatic fibrosis is not known. As a result, we assayed the preventive and therapeutic effects of TJ-9 on experimental hepatic fibrosis, induced in rats by dimethylnitrosamine (DMN) or pig serum (PS), and on rat stellate cells and hepatocytes in primary culture, and assessed the antioxidative activities and the active components of TJ-9. Male Wistar rats were given a single intraperitoneal injection of 40 mg/kg DMN or 0.5 mL PS twice weekly for 10 weeks. In each model, rats were fed a basal diet throughout, or the same diet, which also contained 1.5% TJ-9, for 2 weeks before treatment or for the last 2 weeks of treatment. TJ-9 suppressed the induction of hepatic fibrosis, increased hepatic retinoids, and reduced the hepatic levels of collagen and malondialdehyde (MDA), a production of lipid peroxidation. Immunohistochemical examination showed that TJ-9 reduced the deposition of type I collagen and the number of alpha-smooth muscle actin (alpha-SMA) positive-stellate cells in the liver and inhibited, not only lipid peroxidation in cultured rat hepatocytes that were undergoing oxidative stress, but also the production of type I collagen, alpha-SMA expression, cell proliferation, and oxidative burst in cultured rat stellate cells. In addition, TJ-9 inhibited Fe2+/adenosine 5'-diphosphate-induced lipid peroxidation in rat liver mitochondria in a dose-dependent manner and showed radical scavenging activity. Among the active components of TJ-9, baicalin and baicalein were found to be mainly responsible for the antioxidative activity. These findings suggest that Sho-saiko-to (TJ-9) functions as a potent antifibrosuppressant by inhibition of lipid peroxidation in hepatocytes and stellate cells in vivo.

Antagonism of saikosaponin-induced prostaglandin E2 release by baicalein in C6 rat glioma cells.

There are several Kampo medicines (Chinese herbal medicines) containing both Bupleuri Radix and Scutellariae Radix, which are used for the treatment of inflammation. Saikosaponins are derived from Bupleuri Radix, and baicalein is from Scutellariae Radix. The present study was undertaken to investigate the pharmacological interaction of saikosaponin b1 and baicalein in prostaglandin E2 (PGE2) release from C6 rat glioma cells in vitro. Saikosaponin a, b1 and d potently stimulated PGE2 release, while saikosaponin b2 and c moderately stimulated PGE2 release. Saikosaponin b1 caused an irreversible elevation of intracellular Ca2+ concentration, which was eliminated by removing extracellular Ca2+. On the other hand, baicalein inhibited saikosaponin b1-induced PGE2 release in a concentration-dependent manner. These results suggest that saikosaponins are activators of PGE2 release, and baicalein is one of the functional inhibitors of PGE2 release by saikosaponins.

Expression of the nicotinic acetylcholine receptor alpha4 subunit mRNA in the rat cerebellar cortex.

In order to compare the previous immunohistochemical and immunocytochemical data on the distribution of nicotinic acetylcholine receptor alpha4 subunit-like immunoreactivity with the expression of alpha4 mRNA in the rat cerebellar cortex, the present study determined the cellular distribution of alpha4 mRNA in the rat cerebellar cortex. Northern blot analysis revealed two alpha4 mRNA bands in the rat cerebellum and three in the cerebral cortex, hippocampus, hypothalamus and striatum. The total level of these transcripts was lower in the cerebellum than in the other four regions. The expression of alpha4 mRNA was high in Purkinje cells and granular cells, whereas low expression was detected in the molecular layer. These results suggest that the expression of alpha4 mRNA is closely related to the alpha4-like immunoreactivity in the molecular and Purkinje cell layers. In the granular layer, alpha4 mRNA was very highly and broadly expressed in comparison with the alpha4-like immunoreactivity.

Dose-dependent response of vestibular hair cells of guinea pigs following streptomycin ototoxiation.

Although the involvement of apoptosis has been suggested in the loss of vestibular hair cells due to aminoglycosides, dose-dependent effects of aminoglycosides have not been determined. We therefore examined dose-dependent effects of streptomycin on the degeneration of hair cells of guinea pig ampullar cristae using TUNEL stain and Hoechst nuclear stain. Streptomycin induced apoptosis of hair cells in a dose-dependent manner. Even following high-dose applications, most of the affected cells showed apoptotic features. Apoptosis may therefore play a predominant role in the deletion of vestibular hair cells affected by aminoglycosides.

Allergen-induced synthesis of interleukin-5, but not of IgE, is a key mechanism linked to symptomatic episodes of seasonal allergic rhinitis in sensitized individuals.

Some individuals with detectable levels of Japanese cedar (Criptomeria japonica) pollen-specific immunoglobulin (Ig)E in serum have no apparent nasal symptoms during the pollen season. The response of CD4+ T-helper (Th) cells to the pollen allergen might differ fundamentally between asymptomatic and symptomatic individuals who are already sensitized to the pollen. The aim of this study was to discern the possible differences in responses of peripheral blood mononuclear cells (PBMCs) to the pollen allergen between asymptomatic and symptomatic subjects who have been sensitized to the pollen. This study included 20 non-atopic healthy volunteers (non-atopic group) and 48 patients who had detectable levels of the pollen-specific IgE before the pollen season in 1997. In the review of nasal symptoms during the pollen season 1997, 24 patients had typical symptoms of seasonal allergic rhinitis (symptomatic group), and the remainder had no seasonal aggravation of nasal symptoms (asymptomatic group). Peripheral blood mononuclear cells (1.0 x 10(7) cells/well) were obtained from each individual during the pollen season and cultured in the absence or presence of 12.5 microg of Cry j 1 for 4 days. The concentrations of IgE, interleukin-5 (IL-5), and interferon-gamma (IFN-gamma) in the culture supernatants were measured. The levels of IgE produced by Cry j 1-stimulated PBMCs of the asymptomatic and symptomatic groups were significantly higher than those of the non-atopic group, but did not differ between the asymptomatic and symptomatic groups. The levels of IL-5 produced by Cry j 1-stimulated PBMCs did not differ significantly between the non-atopic group and the asymptomatic group, but the levels of IL-5 were significantly higher in the symptomatic group than in the asymptomatic group as well as the non-atopic group. The levels of IFN-gamma produced by Cry j 1-stimulated PBMCs did not differ significantly among the three groups. In conclusion, our study has suggested that Japanese cedar pollen-induced synthesis of IL-5, but not of IgE or IFN-gamma, is likely to be a key mechanism linked to the symptomatic episode of seasonal allergic rhinitis in individuals sensitized to the pollen.

Seasonal rise in interleukin-4 during pollen season is related to seasonal rise in specific IgE for pollens but not for mites.

Since IL-4 plays a key role in inducing and increasing the generation of not only primary polyclonal but also secondary specific IgE responses by B lymphocytes, a seasonal increase in IL-4 is likely to be involved in such seasonal rises in specific IgE in seasonal allergic rhinitis. The first aim of this study was to investigate the possible seasonal increase in serum IL-4 in patients with seasonal allergic rhinitis due to Japanese cedar pollens. If serum IL-4 increases in response to seasonal pollen exposure and is responsible for the seasonal increase in pollen-specific IgE in sera, this increase in IL-4 might theoretically affect specific IgE synthesis for other allergens. The second aim was to investigate the effect of natural pollen exposure on serum concentrations of house dust mite-specific IgE in patients who have seasonal allergic rhinitis and concurrent perennial allergic rhinitis due to house dust mites. This study included 55 adult patients with seasonal and perennial allergic rhinitis due to Japanese cedar pollens and Dermatophagoides farinae (D. farinae). Venous blood was collected twice from each patient, before and during the cedar pollen season 1996, to determine IL-4, cedar pollen-specific IgE and D. farinae-specific IgE in sera. Both IL-4 and pollen-specific IgE in sera were significantly increased during the pollen season, and the seasonal increase rate in pollen-specific IgE was significantly correlated with the seasonal increase rate in IL-4. By contrast, D. farinae-specific IgE was not changed during the pollen season in these patients. In conclusion, an elevation of IL-4 in sera during the pollen season may play an important part in the seasonal rise in pollen-specific IgE, and enhancement of specific IgE synthesis is likely to need not only an increase in IL-4 but also an increase in the number and/or capacity of specific IgE-secreting B cells.

The clinical role of specific IgE and IgG4 antibodies in patients having immunotherapy for seasonal allergic rhinitis.

This study was designed to investigate the clinical role of specific IgG4 and IgE responses in patients during immunotherapy for seasonal allergy. The study included 109 patients with seasonal allergic rhinitis due to Japanese cedar pollens. They were divided into the control group and the immunotherapy group. Serum samples were obtained at the start of immunotherapy, before the pollen season and during the season, to determine serum specific IgE and IgG4. In the control group specific IgE was significantly increased, but specific IgG4 was not changed during the pollen season. In the immunotherapy group specific IgE was not significantly increased, but specific IgG4 was significantly increased during the season. In the patients having immunotherapy for 2 years or less, the seasonal increase in specific IgG4 related to the magnitude of the clinical effect. In the patients having immunotherapy for 3 years or more, the seasonal increase in specific IgE related to the magnitude of the clinical effect. In conclusion, the specific IgG4 response and specific IgE response during the pollen season make a significant contribution to the clinical effect of immunotherapy. However, modulation of specific IgE and IgG4 responses out of the pollen season was unlikely to be an important phenomenon related to the clinical effect of immunotherapy.