[Show abstract][Hide abstract] ABSTRACT: Anaphylaxis is one of the severest forms of allergic diseases. Some kinds of mushroom are known as causative allergens in food anaphylaxis. Matsutake mushroom (Tricholoma matsutake) is a typical edible mushroom available in autumn in Japan. We encountered an 8-year-old Japanese girl who developed anaphylaxis after ingesting matsutake mushrooms.
We studied the case in detail, by measuring specific IgE antibodies and conducting skin tests, to confirm the diagnosis. We also detected seven cytokines and chemical mediators in the blood in order to study the pathophysiology of the anaphylaxis.
We diagnosed anaphylaxis caused by ingestion of matsutake mushrooms based on the following. A skin prick test showed a positive reaction to matsutake mushroom, and specific IgE antibody for matsutake mushroom extract was detected in the patient's serum by fluorometric ELISA. Blood levels of chemical mediators including histamine, ECP, tryptase and cytokines such as IL-6, IL-5 and IL-10 but not IFN-gamma also increased significantly during the allergic episode.
We demonstrated that chemical mediators including histamine, tryptase and ECP as well as several cytokines were involved significantly during the episode of anaphylaxis. In addition, eosinophils as well as mast cells played significant roles in the anaphylaxis. Furthermore, CD4+CD25+ T regulatory cells that released IL-10 were likely activated during the anaphylaxis. Matsutake mushroom should be considered as a causative allergen in food anaphylaxis.
[Show abstract][Hide abstract] ABSTRACT: Drug-induced hypersensitivity syndrome (HS) is a rare but life-threatening disease. We experienced carbamazepine-induced HS in a 14-year-old boy, who had cefaclor-induced cutaneous eruptions 15 months later. To clarify the mechanisms of HS and the differences between two diseases we studied this case in detail.
We investigated the associated viral agents by polymerase chain reaction and the specific antibodies. We also studied the mechanism of diseases by measuring chemical mediators including cytokines, ECP and immunoglobulins.
The patient was diagnosed as having carbamazepine-induced HS associated with reactivation of human herpesvirus 6 based on the clinical course and laboratory data including drug-induced lymphocyte stimulation tests. Similarly, the diagnosis of cefaclor-induced eruption without any viral reactivation was made. Serum levels of IFN-gamma, IL-6, TNF-alpha, IL-5 and ECP were increased significantly at HS but mildly at cefaclor-induced eruptions. Furthermore, we detected transient hypogammaglobulinemia only at HS.
This is the first report of anticonvulsant-induced HS followed by antibiotic-induced eruptions in a patient. In addition, we demonstrated difference in serum levels of inflammatory cytokines, immunoglobulins, activated eosinophils and viral reactivation between these diseases. This case would contribute to the understanding of the pathophysiology of adverse drug reactions including HS.
Pediatrics International 01/2006; 47(6):616-21. · 0.73 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Adjuvants in vaccines are immune stimulants that play an important role in the induction of effective and appropriate immune responses to vaccine component(s). Diphtheria-tetanus-pertussis (DPT) vaccine contains not only aluminum hydrate (alum) to enhance the immune response to the vaccine ingredients, but also, both for that purpose and as a principal ingredient, pertussis toxin (PT). However, both adjuvants strongly promote T helper (Th) 2 type immune responses. Th1 and Th2 type immune responses are counterbalanced in vivo, and a Th2-prone immune response is not effective against intracellular infections but promotes IgE production, which is related to allergic disease. In this study, we used the CpG motif contained in oligodeoxynucleotide (CpG-ODN), which has an adjuvant effect and also induces the Th1 response, as an adjuvant to this vaccine, and we investigated its adjuvanticity and its potential to modulate immune responses to DPT vaccine. Administration of DPT vaccine with CpG-ODN (DPT-alum/ODN) to mice significantly reduced the total IgE levels and increased the anti-PT specific IgG2a titer in serum, in comparison with ordinary DPT vaccine (DPT-alum). Moreover, we investigated the antibody response to orally administrated ovalbumin (OVA) after vaccine administration. In the DPT-alum/ODN-administered group, the OVA specific IgE production in serum greatly decreased in comparison with that in the DPT-alum-administered group. These data indicate that CpG-ODN was not useful only as an efficient vaccine adjuvant but also shifted the immune responses substantially toward Th1 and modulated the Th1/Th2 immune response in DPT vaccine. These data suggested new applications of CpG-ODN as adjuvants in DPT vaccine.
[Show abstract][Hide abstract] ABSTRACT: In the process of apoptosis, it is known that the transition of cytochrome c from mitochondria into the cytosol occurs, and tumor necrosis factor (TNF)-alpha is one of the molecules responsible for this event. But in the state of hypercytokine induced by D-galactosamine (D-GaIN)/Lipopolysaccharide (LPS), the localization of cytochrome c is little known.
Rats were administrated with D-GaIN(700 mg/kg)/LPS(200 microg/kg). Blood and tissue samples were collected and examined for levels of pro-inflammatory cytokines, the apoptosis of liver cells, and the localization of cytochrome c.
Before administration of D-GaIN/LPS, cytochrome c was definitely localized in the mitochondria. At 2 h after simultaneous administration of D-GaIN/LPS, cytochrome c had accumulated in the cytosol following abrupt increases of plasma TNF-alpha. Massive cell destruction due to apoptosis proved by Terminal deoxynucleo-tidyl transferase-mediated dUTP nick end labeling staining was observed in liver tissue 4 h later and markedly increased levels of cytochrome c were detected in the plasma 12 h after D-GaIN/LPS administration.
Liver injury induced by simultaneous administration of D-GaIN/LPS was closely associated with the production of TNF-alpha, and also with the dynamic movement of cytochrome c from the mitochondria into the cytosol, and then into the systemic circulation. The detection of plasma cytochrome c levels may be a useful clinical tool for the detection of apoptosis in vivo.
Pediatrics International 01/2005; 46(6):685-92. · 0.73 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Abstract Proinflammatory cytokinemia and subsequent endothelial cell activation are the major pathological features of Kawasaki disease (KD), which progresses to systemic vasculitis and results in coronary artery lesions (CALs). We studied the serum levels of proinflammatory cytokines and of the soluble receptors before and after intravenous gamma-globulin (IVGG) treatment to investigate whether the anti-inflammatory effect of IVGG was due to the reduction of increased serum levels of their cytokines and soluble receptors. In the acute phase of KD, the serum levels of interleukin (IL)-2 and IL-5, as well as those of IL-6, IL-10, and interferon-γ, were markedly higher than those in controls. The level of tumor necrosis factor-α was higher than that in the control, but the difference was slight and not significant. The soluble IL-6 receptor levels were lower than those of the controls. After IVGG administration, the increased levels of these cytokines and soluble receptors were abruptly down-regulated to within their normal ranges. The patients enrolled in the present study were all effectively treated with IVGG, without a steroid, and improved without any residual CALs. Overall, IVGG administration to patients with KD was found to be effective in reducing inflammatory processes and in preventing CALs, and was followed by reduction of the serum levels of the proinflammatory cytokines and their receptors.
Modern Rheumatology 12/2004; 14(6):447-452. · 2.21 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: In order to predict the late-development of chronic lung disease of prematurity (CLD), cytokines in the cord blood were assessed in this study.
Eighteen premature infants with CLD were enrolled. Cord blood plasma levels of cytokines of these infants and 12 control infants without CLD were measured including interleukin (IL)-1beta, IL-2, IL-4, IL-6, IL-8, IL-10, interferon (IFN)-gamma, tumor necrosis factor (TNF)-alpha, soluble TNF receptor-I, and soluble IL-6 receptor using a cytometric bead array and an enzyme-linked immunosorbent assay.
The cord blood IL-6, IL-8, and sTNFR-I levels were significantly elevated in CLD infants compared with those in control (P < .05). IL-1beta, IL-2, IL-4, IL-10, and IFN-gamma were undetectable in both groups. CLD infants with maternal chorioamnionitis had higher IL-6 than those without chorioamnionitis (P < .01). In CLD infants, IL-6 was higher in the infants who required prolonged oxygen therapy (P < .05).
Elevated inflammatory cytokines in the cord blood are associated with the progression to CLD.
American Journal of Obstetrics and Gynecology 11/2004; 191(5):1649-54. · 3.97 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: We analyzed the effects of three therapies on 30 patients with childhood systemic lupus erythematosus, and classified the patients into three groups. The therapies were as follows; Group A (8 cases), methylpredni-solone (mPSL) pulses plus oral prednisolone (PSL) alone, Group B (10 cases), mPSL pulses plus oral PSL and mizoribine (MZB) or azathioprine (AZP), Group C (12 cases), mPSL pulses and intravenous cyclophosphamide (IVCY) pulse therapy plus oral PSL and MZB or AZP. Three years after treatment, we compared the laboratory data (C3, C4, CH50 and anti-DNA antibody), the SLEDAI scores and numbers of relapses in these three groups. We demonstrated that group C had the best data, and this data indicated that the median C3, C4 and CH50 increased and that the median anti-DNA antibody and the mean of the numbers of relapses decreased. In conclusion, the combination of immunosuppressants and IVCY appeared to offer great benefits in childhood systemic lupus erythematosus.
[Show abstract][Hide abstract] ABSTRACT: Three cases of childhood-onset systemic lupus erythematosus (childhood SLE) with long-term remission are reported. These cases were not complicated with collagen diseases and had no SLE disease activity index scores either 3 or 5 years after onset. We suggest that some patients with childhood SLE may be able to abandon the maintenance therapy, and that careful observation is needed for each individual case. Uniform remission criteria based on clinical trials are needed.
Modern Rheumatology 08/2003; 13(3):285-287. · 2.21 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Immune activation and generalized vasculitis are two central features of Kawasaki disease (KD). Recent observations indicated that serum levels of cytokines including interferon(INF)- γ, tumor necrosis factor (TNF)- α and interleukin (IL)-1 are remarkably increased, and that the administration of intravenous γ-globulin (IVGG) reduces the levels of elevated cytokines. Objective: We examined whether the plasma exchange (PE) for intractable KD cases reduces the elevated serum cytokines, and whether hypercytokinemia is originated from peripheral mononuclear cells at acute phase. Materials and Methods: We first compared the serum levels of cytokines between pre- and post-treatment of IVGG (8 cases) and PE (8 cases), using ELISA and cytometric bead array (CBA) system (Becton & Dickinson). For 4 cases among them, we investigated the messenger RNA levels of several cytokines in peripheral mononuclear cells at acute phase, using ribonuclease protection assay (RPA) system (Becton & Dickinson). Results: In sera of the children intractable to IVGG, increased levels of cytokines were detected such as INF-γ, IL-6, IL-10 and soluble TNF receptor (sTNFR). After PE therapy, serum levels of them markedly decreased to the normal ranges (INF-γ: 9.1 ± 13.4 4.0 ± 6.4 pg/ml, IL-6: 67.5 ± 74.36.6 ± 8.4 pg/ml, IL-10: 14.1 ± 5.17.4 ± 2.1 pg/ml, sTNFR: 2521.9 ± 728.21338.2 ± 575.9 pg/ml). However, RPA analysis demonstrated that messenger RNA levels of several cytokines at acute phase were undetectable in both pre- and post-treatment of PE in peripheral mononuclear cells. Discussion: These findings suggested that the effectiveness of IVGG and PE treatment for KD will be attributed to the reduction of proinflammatory cytokine levels in serum, and that the increased levels of proinflammatory cytokines were originated not from the circulating mononuclear cells, but presumably from in situ lymphocytes and macrophages located at inflammatory lesion such as vasculitis lesion.
Pediatric Research 01/2003; 53(1):172-172. · 2.84 Impact Factor