Biomedical subjects

Y Kakinoki

Publications and source records attributed to Y Kakinoki.

At least 37 records · Page 2Linked to original sources

PubMed1998

Allergen-specific immunotherapy for allergic rhinitis: a new insight into its clinical efficacy and mechanism.

Immunotherapy has been used widely for allergic diseases for more than 90 years but, in the opinion of many physicians, it is still a controversial form of treatment. The exact mechanism of action of immunotherapy remains to be determined. In the present study, we review the clinical efficacy and mechanism of action of immunotherapy for allergic rhinitis. Recent double-blind placebo-controlled studies have demonstrated the clinical efficacy of immunotherapy for allergic rhinitis. This therapeutic method has several advantages over conventional pharmacological treatment. Immunotherapy is inferior to pharmacological treatment in the short term, but in the long term it is substantially superior with respect to clinical efficacy. Immunotherapy has the potential permanently to alleviate the abnormal immunological responses of allergic rhinitis and to cure the nasal symptoms in the long term, even after discontinuation of injections. In addition, immunotherapy can prevent the onset of new sensitizations in allergic patients and may prevent the progression of rhinitis to asthma. It may therefore be possible for immunotherapy to alter the natural history of allergic sensitization and its clinical manifestation. These lines of clinical evidence could affect strategies of long-term therapy for allergic rhinitis. Modern molecular biological techniques have suggested that immunotherapy may affect allergen-induced TH responses or cytokine profiles, but there is no general agreement among investigators. However, IL-5 is likely to be the most important cytokine involved in the clinical efficacy of immunotherapy, and the suppression of allergen-induced IL-5 synthesis is most likely to be involved in the mechanism of immunotherapy. Our recent investigations, focusing on specific IgE and IgG4 responses, suggest that immunotherapy-induced changes in these specific antibodies play a clinical role and are involved in the mechanism of action of immunotherapy. It is probable that immunotherapy modulates and affects many different immunological and non-immunological phenomena to produce clinical efficacy and that clinical improvement is a consequence of different mechanisms over time.

Allergens↗

PubMed1998

Roxythromycin reinforces epithelial defence function in rabbit trachea.

Our study elucidates the effect of roxythromycin (RXM) on airway epithelial defence functions, especially the mucociliary and epithelial barrier functions, in the rabbit trachea. In vitro ciliary activity was not affected in the presence of 3.3 mg/ml of RMX, but was enhanced in the presence of 6.7 mg/ml of RXM. Oral administration of 10 and 100 mg of RXM for 14 days enhanced both ciliary activity and mucociliary transport velocity in the trachea. Epithelial permeability to fluorescein isothiocyanate-dextrans (FD-70s; molecular weight: 70,000 daltons) was not affected by oral administration of 10 mg of RXM for 14 days, but was significantly reduced by oral administration of 100 mg of RXM for 14 days. Inhalation of platelet activating factor (PAF) compromised the function of the mucociliary system and the tight junction barrier. However, pretreatment with 20 mg of RXM significantly alleviated the PAF-induced decrease in mucociliary function and the increase in epithelial permeability to FD-70s. In conclusion, such reinforcement of the epithelial defence functions is likely to be involved in the pharmacological action underlying the clinical efficacy of RXM for chronic airway inflammatory disease.

Animals↗

PubMed1998

Immunotherapy decreases seasonal rise in serum-soluble CD23 in seasonal allergic rhinitis.

There is increasing in vitro evidence that soluble CD23 (sCD23) is capable of potentiating IgE synthesis, but the in vivo physiologic significance remains to be established. This study investigated the seasonal changes in sCD23 in patients with seasonal allergic rhinitis. It included 112 adult patients with seasonal allergic rhinitis due to Japanese cedar pollens and 20 nonatopic healthy volunteers. The 64 patients of the pharmacotherapy group were treated with nonsedating antihistamine tablets alone throughout the pollen season and the remaining 48 patients of the immunotherapy group continued to be treated with immunotherapy. Serum concentrations of sCD23 were measured in each patient, before and during the pollen season of 1996, by a sandwich enzyme-linked immunosorbent assay. The serum levels of sCD23 in the pharmacotherapy group before the pollen season were significantly higher than those in the nonatopic group (P = .0130) and those in the immunotherapy group (P = .0316). Seasonal increase in sCD23 was significant in the pharmacotherapy group, irrespective of the clinical response (P < .0001). By contrast, sCD23 was not significantly increased in the good responders to immunotherapy (P = .1826), but was significantly increased in the poor responders to immunotherapy (P = .0052). A significant correlation between seasonal increase in rate in specific IgE and seasonal increase in rate in sCD23 was confirmed in both the pharmacotherapy group (rs = 0.321, P = .0107) and the immunotherapy group (rs = 0.474, P = .0012). In conclusion, seasonal rise in sCD23 is associated with and is probably involved in seasonal rise in specific IgE in patients with seasonal allergic rhinitis, and successful immunotherapy is capable of blunting seasonal increase in sCD23, thus resulting in attenuation of seasonal increase in specific IgE and clinical benefits during the pollen season.

Adult↗

PubMed1998

Influence of the allergic response on the mucociliary system in the eustachian tube.

The effect of systemic and local allergic responses on the mucociliary system of the Eustachian tube was investigated. Egg albumin was administered to guinea pigs via the jugular vein to evoke systemic anaphylaxis in animals previously sensitized with egg albumin. Ciliary activity in the Eustachian tube of sensitized animals was significantly higher than that of control animals. However, the mucociliary clearance time of the Eustachian tube in sensitized animals was significantly longer than in control animals. Local allergic response induced by intratympanic instillation of (BPO)61-BGG induced cilioexcitation and prolonged mucociliary clearance in the guinea pigs sensitized with BPO-BGG. A partial loss of the inner layer of the mucus blanket of the Eustachian tube was observed under electron microscopy. In conclusion, the systemic as well as the local allergic response accelerates ciliary activity but may affect the mucus blanket and induce mucociliary dysfunction in the Eustachian tube, resulting in a predisposition to middle ear diseases.

Allergens↗

PubMed1998

A comparative study of the clinical efficacy of immunotherapy and conventional pharmacological treatment for patients with perennial allergic rhinitis.

This study was designed to compare the clinical outcome of prolonged immunotherapy for perennial allergic rhinitis with that of pharmacological treatment. Patients with perennial allergic rhinitis due to Dermatophagoides farinae (D. farinae) were divided into two groups; a pharmacotherapy group and an immunotherapy group. The pharmacotherapy group was treated with conventional pharmacological treatment using antihistamine tablets and topical steroid sprays and the immunotherapy group was treated with D. farinae extracts for 5 successive years. None of symptom scores at enrollment differed significantly between the groups. At 6 months and 1 year after the start of treatment the rate of decrease in each score was significantly greater in the pharmacotherapy group than in the immunotherapy group. The rate of decrease in sneezing scores, but not in the other scores, at 2 years after the start of treatment was also greater in the pharmacotherapy group than in the immunotherapy group. However, at 3 years the rate of decrease in any of the scores did not differ significantly between groups. The differences between the groups became clear-cut again after 5 years of treatment, when the rate of decrease in all of the scores was significantly greater in the immunotherapy group than in the pharmacotherapy group. Therefore, short-term treatment with pharmacological agents is probably superior to immunotherapy but, in the long-term, immunotherapy is apparently superior to pharmacological treatment with respect to clinical efficacy. In addition, prolonged immunotherapy provided long-term clinical efficacy and might provide a long-standing cure even after discontinuation of the therapy. In a questionnaire interview, approximately half of patients were very satisfied with prolonged immunotherapy and three-quarters were fairly satisfied or more. Additionally, the magnitude of improvement in nasal stuffiness contributed significantly and exclusively to the patient evaluation of immunotherapy. We propose that prolonged immunotherapy is never inferior to anti-allergenic pharmacological treatment and that it is possible to achieve long-term clinical efficacy or long-standing cure even after the discontinuation of immunotherapy, and that patients with perennial allergic rhinitis will be very satisfied with this prolonged therapeutic technique if nasal stuffiness is considerably alleviated.

Adolescent↗

PubMed1998

Risk factors for adverse systemic reactions occurring during immunotherapy with standardized Dermatophagoides farinae extracts.

The most serious problem in practical immunotherapy is the risk of occasional, potentially life-threatening adverse systemic reactions. Elucidation of the incidence of, and possible risk factors for, systemic reactions would have a profound effect on the decision about how to manage allergic rhinitis. The aim of this retrospective study was to document the incidence and risk factors of adverse systemic reactions during immunotherapy using standardized Dermatophagoides farinae (D. farinae) extracts for perennial allergic rhinitis. This study included 386 patients (22,722 injections) with perennial allergic rhinitis who had received immunotherapy with standardized D. farinae extracts in our clinics for the past 5 years. The incidence of systemic reactions was 6.22% per patient and 0.12% per injection. The time of onset of systemic reactions ranged from 3 to 30 min (mean 11.3 min) after injections. Our study has demonstrated that asthma, atopic dermatitis and a high level of IgE in serum, but not a high level of specific IgE in serum, are important high risk factors that may induce severe adverse systemic reactions in patients who receive immunotherapy for perennial allergic rhinitis. The incidence of systemic reactions in those who had a high level of IgE (higher than 1000 U/ml) and asthma and/or atopic dermatitis was 66.67% (12/18) per patient. Conversely, the incidence of systemic reactions in those who had none of the risk factors was 1.64% per patient. Thus, the rate of systemic reactions is thought to be reduced by 75% if patients with high risk factors are strictly excluded from immunotherapy for allergic rhinitis.

Allergens↗

PubMed1998

The herbal medicine shoseiryu-to inhibits allergen-induced synthesis of tumour necrosis factor alpha by peripheral blood mononuclear cells in patients with perennial allergic rhinitis.

The herbal medicine shoseiryu-to is an effective agent in the treatment of allergic rhinitis. However, the mechanism by which it exerts its action in improving patient symptoms remains unclear. It might affect the allergen-induced TH1 and/or TH2 responses. This study investigated whether the herbal medicine could affect cytokine synthesis by peripheral blood mononuclear cells (PBMCs) in response to the major Dermatophagoides farinae (D. farinae) allergen, Der f 1. PBMCs were obtained from 15 patients with perennial allergic rhinitis due to D. farinae, and were stimulated for 96 h with 10 micrograms/ml Der f 1 in the presence or absence of 45 mg/ml shoseiryu-to. The culture supernatants were harvested to determine the synthesis of IgE, interleukin 5 (IL-5), IL-6, IL-10, interferon-gamma (IFN-gamma) and tumour necrosis factor alpha (TNF-alpha). The agent did not affect the allergen-induced synthesis of IL-5, IL-6 and IFN-gamma, but somewhat decreased the synthesis of IgE and IL-10. This study highlighted an interesting pharmacological action of shoseiryu-to to substantially inhibit the allergen-induced synthesis of TNF-alpha. Our study suggests that the shoseiryu-to may alleviate nasal symptoms in allergic rhinitis through control of the allergen-induced inflammatory process.

Allergens↗

PubMed1998

Suplatast tosilate affects the initial increase in specific IgE and interleukin-4 during immunotherapy for perennial allergic rhinitis.

Suplatast tosilate can inhibit IL-4 production and suppress IgE synthesis in vitro. However, the theory that the agent causes changes in production of IL-4 and IgE in vivo has little experimental support. Immunotherapy could decrease the specific IgE response, but such a favourable effect is only possible with prolonged therapy after an initial increase in specific IgE. The use of suplatast tosilate together with immunotherapy may blunt the initial rise in specific IgE and decrease serum levels of specific IgE more quickly. Eighty-three adult patients with perennial allergic rhinitis due to Dermatophagoides farinae (D. farinae) were treated for 6 months with one of 3 treatments. Seventeen patients were treated with oral administration of 300 mg/day suplatast tosilate alone. Forty-six patients were treated with immunotherapy using standardized D. farinae alone. Twenty patients were treated with immunotherapy together with concurrent oral administration of 300 mg/day suplatast tosilate. Serum samples were collected 3 times from each patient, at enrollment, at 3 months and at 6 months after enrollment. Oral administration of suplatast tosilate for 3 and 6 months significantly decreased serum levels of IL-4 and specific IgE, and the rate of decrease in specific IgE correlated significantly with the rate of decrease in IL-4. The rates of decrease in IL-4 and specific IgE at 3 and 6 months were significantly greater in the patients treated with suplatast tosilate and immunotherapy than in those treated with immunotherapy alone. In conclusion, suplatast tosilate is able significantly to decrease serum levels of IL-4 and specific IgE, and the use of the drug together with immunotherapy can blunt the initial increase in specific IgE during the first 6 months of immunotherapy.

Adult↗

PubMed1998

Cry j 1-induced synthesis of interleukin-5 and interferon-gamma by peripheral blood mononuclear cells of patients with seasonal allergic rhinitis due to Japanese cedar pollens.

This study comprised 130 adult patients with Japanese cedar pollen-specific IgE in the serum and 15 non-atopic individuals. Eighteen patients had no seasonal aggravation of nasal symptoms during the pollen season in 1998 (asymptomatic group). Forty-two patients had not been treated previously with immunotherapy and were treated with antihistamine tablets during the pollen season in 1998 (medication group). Sixty-one patients had undergone variable periods of immunotherapy using pollen extracts, and they were further divided into a good-IT group who responded markedly to immunotherapy and a poor-IT group who responded poorly to immunotherapy. The remaining nine patients had been treated with immunotherapy for more than 12 years and all of them had stopped immunotherapy by the end of May 1997 because they had no nasal symptoms for the last three pollen seasons and were considered to be cured of seasonal allergic rhinitis (cure group). Peripheral blood mononuclear cells (PBMCs) were collected from each subject during the cedar pollen season in 1998 and were stimulated for 96 h with 10 micrograms/ml Cry j 1. The concentrations of interleukin-5 (IL-5) and interferon-gamma (IFN-gamma) in the culture supernatant were determined using an enzyme-linked immunosorbent assay. The levels of IFN-gamma did not differ significantly among the non-atopic group, the asymptomatic group, the medication group, the poor-IT group and the good-IT group. The level of IL-5 in the asymptomatic group was not different from that in the non-atopic group. The levels of IL-5 in the medication group, the good-IT group and the poor-IT group were significantly higher than in the non-atopic group. The level of IL-5 in the good-IT group, but not in the poor-IT group, was significantly lower than in the medication group. The level of IL-5 in the cure group was not significantly different from in the non-atopic group, and the level of IFN-gamma in the cure group was significantly lower than in the non-atopic group. In conclusion, immunotherapy can decrease the pollen allergen-induced synthesis of IL-5, but not of IFN-gamma, and this immunological modulation is involved in the working mechanism of immunotherapy related to its clinical efficacy. A tolerance or anergy of both TH1 and TH2 cells under allergen stimulation may be an immunological indication of cure after the treatment of seasonal allergic rhinitis. Thus, the suppression of synthesis of IL-5 and IFN-gamma by allergen-stimulated PBMCs is likely to be a reliable criterion for a possible cure of seasonal allergic rhinitis after immunotherapy.

Adult↗

PubMed1998

Seasonal increase in specific IgE in serum induced by natural Japanese cedar pollen exposure in asymptomatic and symptomatic sensitized individuals.

The aim of this study was to determine whether there is a difference in the specific IgE response to pollen exposure between asymptomatic and symptomatic subjects who were already sensitized to Japanese cedar pollen. Sixty-four subjects with detectable serum levels of cedar pollen-specific IgE, which were apparent even before the pollen season in 1997, were enrolled in the study. Thirty-five had typical symptoms of seasonal allergic rhinitis during the pollen season in 1997 (symptomatic group) and the remainder had no seasonal aggravation during the pollen season in 1997 (asymptomatic group). Serum samples were collected twice from each subject, before and during the pollen season in 1997, to determine specific IgE by the lumiward immunoassay system. In both groups, the serum levels of specific IgE during the pollen season were significantly higher than those before the pollen season, and the rates of seasonal increase in specific IgE did not differ significantly between the groups. In conclusion, the specific IgE response during the pollen season is not a hallmark of clinical allergy and does not discriminate between symptomatic and asymptomatic individuals sensitive to the pollen.

Allergens↗

PubMed1998

Clinical evaluation of lumiward immunoassay system for detection of specific IgE associated with allergic rhinitis.

The detection of specific IgE is a critical prerequisite for both the definitive diagnosis and the therapeutic strategy of allergic rhinitis and other allergic disorders. The aim of the present study was thus to evaluate the clinical significance of the solid phase capture system (CAP) and the lumiward immunoassay system (LMD) in the diagnosis of allergic rhinitis due to Dermatophagoides farinae (D. farinae) and Japanese cedar (Cryptomeria japonica) pollens. The specificity of both the CAP and the LMD in the detection of D. farinae-specific IgE and Japanese cedar pollen-specific IgE was 100%. The sensitivity to detect D. farinae-specific IgE was 95.76% in the skin test, 86.53% in the CAP and 88.53% in the LMD, respectively. The combination of the nasal provocation test and the CAP substituted for the skin test resulted in correct diagnoses for 98.25% of the patients, and the combination of the nasal provocation test and the LMD substituted for the skin test resulted in correct diagnoses for 98.00% of the patients. Therefore, the diagnostic significance of the LMD for perennial allergic rhinitis is likely to be equal to that of the CAP. The sensitivity to detect Japanese cedar pollen-specific IgE was 94.50% in the skin test, 84.47% in the CAP, and 96.76% in the LMD, respectively. The sensitivity of the CAP in the detection of Japanese cedar pollen-specific IgE was inferior to that of the skin test, but the sensitivity of the LMD in the detection of pollen-specific IgE was somewhat superior to that of the skin test. In addition, the combination of the nasal provocation test and the CAP substituted for the skin test resulted in correct diagnoses for 98.38% of the patients, whereas the combination of the nasal provocation test and the LMD substituted for the skin test resulted in correct diagnoses for 100% of the patients. Therefore, the diagnostic significance of the LMD for seasonal allergic rhinitis due to Japanese cedar pollens is probably larger than that of the CAP. In conclusion, the LMD may be a better "gold standard" for the detection of Japanese cedar pollen-specific IgE than the skin test, and the combination of the nasal provocation test and the LMD is a better diagnostic tool for the detection of Japanese cedar pollen-induced seasonal allergic rhinitis than the combination of the nasal provocation test and the skin test or the CAP.

Allergens↗

PubMed1998

Nitrogen dioxide compromises defence functions of the airway epithelium.

The effect of nitrogen dioxide (NO2) exposure on airway epithelial defence functions, such as ciliary activity, mucociliary transport velocity and junctional barrier function, remains to be elucidated. Our study investigates the effect of 24-h exposure to 3.0 ppm of NO2 on the airway epithelial defence functions in the healthy rabbit. Fifty-two healthy rabbits were exposed to 3.0 ppm of NO2 (NO2 group) or pure air (control group) for 24 successive hours in exposure chambers. After completion of the exposure sequence, the ciliary activity in the trachea was examined by a photoelectric method, the mucociliary transport velocity in the trachea by an endoscopic method and epithelial permeability of the trachea to fluorescein isothiocyanate-dextrans (FD-70s; molecular weight: 70,000 daltons) by an in vitro tracheal sac method. In the NO2 group, all epithelial defence functions, including ciliary activity, mucociliary transport velocity and epithelial permeability were significantly inferior to those in the control group. Although there was considerable overlap in the parameters examined between the two groups, approximately two-thirds of the animals were susceptible to 24-h exposure to 3 ppm of NO2. Dysfunction of both the junctional barrier and the mucociliary system could allow easier entry of allergen molecules to the airway parenchyma, where immunocomponent cells exist. NO2 might be involved to some extent in the clinical manifestation of airway allergic disorders through epithelial dysfunction.

Air Pollutants↗

PubMed1997

Multisite phosphorylation and the nuclear localization of phosphatase inhibitor 2-green fluorescent protein fusion protein during S phase of the cell growth cycle.

Human phosphatase inhibitor 2 (Inh2) is a phosphoprotein that complexes with type 1 protein phosphatase, and its expression peaks during S phase and mitosis during the cell cycle. Localization of Inh2 was visualized in HS68 human fibroblasts by fusing Inh2 to green fluorescent protein (GFP). During G1 phase, Inh2-GFP was localized in the cytoplasm, and as cells progressed into S phase Inh2-GFP accumulated in the nucleus. Known phosphorylation sites of Inh2 at Thr-72, Ser-86, and Ser-120/121 were each replaced with alanine. None of the mutated Inh2-GFP proteins accumulated in the nucleus during S phase, indicating that all of these phosphorylation sites were required. Mutation of two lysine residues in a putative nuclear localization sequence in Inh2 also prevented the Inh2-GFP fusion protein from accumulating in the nucleus during S phase. Recombinant Inh2 was phosphorylated by kinases in cytosols prepared from G1 and S phase cells. The amount of Inh2 kinase attributed to casein kinase 2, based on inhibition by heparin, increased 2.6-fold from G1 to S phase. In addition, kinases in G1 versus S phase cytosols produced distinct Inh2 phosphopeptides. The results indicate that changes in phosphorylation of Inh2 are involved in intracellular redistribution of the protein during the cell cycle.

Amino Acid Sequence↗

PubMed1997

Platelet activating factor compromises airway epithelial defense functions.

BACKGROUND: The mechanism of disruption of the epithelial defense function observed in asthmatic airways is considered to be largely the result of mediators involved in allergic responses. Platelet activating factor (PAF) might be a key mediator involved in this mechanism. OBJECTIVE: This study was designed to determine whether PAF is capable of compromising the epithelial defense functions, such as tight junctional barriers and the mucociliary system. METHODS: A total of 120 healthy rabbits were used. Twenty of them were used as normal controls. Eighty rabbits were treated with inhalation of 10 ml of PAF (200 microg/ml), and 20 animals were used for the examination of epithelial defense functions of the trachea at 1, 10, 20, and 30 days after inhalation of PAF. Epithelial defense functions of the trachea were evaluated by ciliary activity, mucociliary transport velocity, epithelial permeability to fluorescein isothiocyanate dextrans (70,000 d), and electron microscopy of the epithelial structure. RESULTS: PAF inhalation induced a significant decrease in ciliary activity and mucociliary transport velocity, which persisted for up to 20 days. PAF inhalation also caused a significant 7.4-fold increase in epithelial permeability to fluorescein isothiocyanate dextrans at I and 10 days. This increased epithelial permeability returned to the normal level 20 days after PAF inhalation. However, electron microscopy demonstrated no apparent evidence of epithelial shedding. CONCLUSIONS: PAF-induced prolonged dysfunction of both the epithelial junctional barrier and the mucociliary system may allow enhanced entry of allergen molecules, as well as bronchoactive agonists to the airway parenchyma and may also significantly contribute to an increased airway responsiveness.

Administration, Inhalation↗

PubMed1997

Serum levels of specific IgE, soluble interleukin-2 receptor, and soluble intercellular adhesion molecule-1 in seasonal allergic rhinitis.

BACKGROUND: There is increasing evidence that soluble interleukin-2 receptor (sIL-2R) might reflect T cell activation in vivo and soluble intercellular adhesion molecule-1 (sICAM-1) might reflect the ongoing inflammatory response in the inflamed site. OBJECTIVE: The aim of this study was to determine the effect of antihistamine tablets and allergen-specific immunotherapy on the seasonal changes in specific IgE, sIL-2R, and sICAM-1 in the serum of patients with seasonal allergic rhinitis. METHODS: This prospective study included 99 patients with seasonal allergic rhinitis due to Japanese cedar pollens and 27 nonatopic healthy volunteers. The patients were divided into an antihistamine-treated group and an immunotherapy group. Serum samples were collected before and during the pollen season from each patient to determine specific IgE, sIL-2R, and sICAM-1. RESULTS: Levels of sIL-2R before the pollen season did not differ significantly among the nonatopic group, the antihistamine-treated group, and the immunotherapy group. The levels of sICAM-1 before the pollen season were significantly higher in the antihistamine-treated group and in the immunotherapy group than in the nonatopic group. Seasonal increase in specific IgE was significant in the antihistamine-treated group regardless of their clinical outcomes. In contrast, significant increase in specific IgE was observed during the pollen season in poor responders but not in good responders to immunotherapy. Serum levels of sIL-2R and sICAM-1 were significantly increased during the pollen season in poor responders of the antihistamine-treated group and the immunotherapy group. On the other hand, neither seasonal increase in sIL-2R nor sICAM-1 was significant in good responders of the antihistamine-treated group and the immunotherapy group. CONCLUSIONS: Serum levels of sICAM-1 are higher in patients with seasonal allergic rhinitis, even outside of the pollen season when the allergen does not naturally exist. Seasonal changes in serum sICAM-1 as well as sIL-2R and specific IgE are probably objective markers to indicate the clinical efficacy of antihistamines and immunotherapy on seasonal allergic rhinitis.

Adult↗

PubMed1997

The effect of immunotherapy on the serum levels of eosinophil cationic protein in seasonal allergic rhinitis.

The role of serum eosinophil cationic protein levels in allergic rhinitis is controversial. It is also unclear whether with immunotherapy it is possible to reduce these serum levels in allergic diseases. We studied serum eosinophil cationic protein levels in patients with cedar-induced allergic rhinitis and compared them with non-atopic controls. The second aim of this study was to elucidate whether immunotherapy is capable of decreasing the seasonal elevation in serum eosinophil cationic protein levels in seasonal allergic rhinitis. The serum eosinophil cationic protein levels of the untreated patient group were significantly higher than those of the non-atopic controls. The levels in patients who received immunotherapy for 2 yr were also significantly higher than those of the non-atopic controls. However, the levels were not different between the patients undergoing immunotherapy for over 3 yr and the non-atopic controls. The serum levels of the 31 patients treated with immunotherapy correlated with the duration of immunotherapy. In conclusion, the serum eosinophil cationic protein levels are higher in untreated patients with seasonal allergic rhinitis and this seasonal activation in circulating eosiohophils decreases gradually during immunotherapy, but this inhibitory effect becomes apparent only after a number of years of immunotherapy. This prevention of seasonal eosinophil activation is one of the mechanisms responsible for the clinical effect of immunotherapy.

Adolescent↗

PubMed1997

Serum level of soluble interleukin-2 receptor in patients with seasonal allergic rhinitis.

The rate of release of the soluble form of interleukin-2 receptor (soluble IL-2R) reflects T cell activation in vivo. Since T lymphocytes play a central role in respiratory allergic disorders, the measurement of serum levels of soluble IL-2R may be useful in analysing the disease state of allergic disorders. The study has aimed at investigating the seasonal changes in serum soluble IL-2R in 81 patients with seasonal allergic rhinitis due to Japanese cedar pollens, with special reference to the effect of anti-allergic pharmacotherapy and immunotherapy. Serum samples were obtained twice from each patient, before and during the pollen season, and all the serum samples were simultaneously used for determination of soluble IL-2R and cedar pollen-specific immunoglobin E (IgE). Seasonal elevation in soluble IL-2R was not associated with the good clinical outcome but was associated with the poor clinical outcome, irrespective of pharmacotherapy or immunotherapy. Additionally, successful immunotherapy suppressed seasonal elevation of serum soluble IL-2R more strongly than successful pharmacotherapy, and seasonal increase rates in soluble IL-2R were inversely correlated with the duration of immunotherapy. Seasonal increase rates in soluble IL-2R were significantly correlated with seasonal increase rates in specific IgE in both the medication group and the immunotherapy patients. These results may suggest that seasonal changes in serum soluble IL-2R may serve as an indicator for clinical outcome of seasonal allergic rhinitis, that the magnitude of T cell activation could affect specific IgE production, and that T cell activation could be gradually modulated as immunotherapy proceeds. In conclusion, seasonal changes in serum soluble IL-2R may serve as an objective indicator for clinical outcome of seasonal allergic rhinitis.

Adolescent↗

PubMed1997

Immunotherapy affects the seasonal increase in specific IgE and interleukin-4 in serum of patients with seasonal allergic rhinitis.

This study was designed to determine seasonal changes in cytokines, soluble CD23 and specific IgE in the serum of patients with seasonal allergic rhinitis, and the effect of immunotherapy on these seasonal changes. Fifty-four patients with seasonal allergic rhinitis caused by Japanese ceder pollens were divided into a medication group and an immunotherapy group. The patients of the medication group were treated with non-sedating antihistamines alone during the pollen season. The patients of the immunotherapy group had been treated for variable periods (mean, 5.0 +/- 3.2 years) with immunotherapy using japanese cedar pollen antigens. Serum samples were collected before and during the pollen season from each patient, to determine specific IgE, interleukin-4 (IL-4), interferon-gamma (IFN-gamma) and soluble CD23 levels in serum. A significant increase in specific IgE and IL-4 and a significant decrease in IFN-gamma were observed during the pollen season in the medication group. In contrast, in the immunotherapy group, none of specific IgE, IL-4 and IFN-gamma was significantly changed following natural exposure to pollens. However, these effects were not significant in patients undergoing immunotherapy for 3 or fewer years. Seasonal rates of increase in specific IgE and IL-4 differed significantly between good responders and poor responders to immunotherapy, but seasonal rates of decrease in IFN-gamma did not. A seasonal rate of increase in soluble CD23 was significantly correlated with a seasonal rate of increase in specific IgE, in both the medication and the immunotherapy groups. The seasonal rate of increase in soluble CD23 was significantly smaller in the good responders than in the poor responders to immunotherapy. In conclusion, pollen immunotherapy reduces the seasonal increase in specific IgE, IL-4 and soluble CD23 in serum, and in addition switches the seasonal preferential activation of Th-2 cells to reciprocal activation of Th-1 cells with treatment over several years. It is likely that the mechanisms responsible for the clinically beneficial effects of immunotherapy principally involve the modulation of Th-2 rather than Th-1 cytokines.

Adult↗