Recent large-scale sequencing of the human genome has facilitated novel gene discovery. A novel gene, ML-1 (interleukin (IL)-17F), was identified from a human expressed sequence tag (EST) sequence, a genomic DNA clone and T cell cDNA sequences. It was found that ML-1 shares significant sequence identity and functional similarity with the gene encoding IL-17A, but a distinct functional property for ML-1 has been demonstrated. While limited information is currently available, recent functional studies have suggested that ML-1 (IL-17F) is a multifunctional protein with a wide tissue expression pattern. In particular, the potent proinflammatory action of ML-1 (IL-17F) identified thus far, together with its association with asthma, suggests that ML-1 (IL-17F) may have a significant role in the regulation of airway inflammatory processes.

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Background: Interleukin (IL)-18 acts as both a Th1 and Th2 cytokine, but its association with allergic diseases remains unclear. The aim of the present study was to measured plasma IL-18 and serum IgE levels in atopic children to evaluate how IL-18 is associated with allergic diseases.
Methods: The plasma IL-18 and serum IgE levels in 51 atopic children, 28 healthy control children and 14 healthy control adults were measured by enzyme-linked immunosorbent assay (ELISA). The 5' end of the IL-18 gene of 48 atopic children and 20 healthy control children was sequenced.
Results: The plasma IL-18 level was significantly elevated in children with bronchial asthma and/or atopic dermatitis. Plasma IL-18 levels in the moderate or severe atopic dermatitis group were significantly higher than those in either the control group or the mild atopic dermatitis group. There was a positive correlation between plasma IL-18 and serum IgE levels. Three allelic combinations of polymorphisms in the IL-18 gene promoter region were observed. There was no significant difference in the plasma IL-18 levels between groups carrying these genotypes. However, bronchial asthma patients had significantly higher frequencies of the -137 G/G genotype than did control children.
Conclusions: The plasma IL-18 level was elevated, particularly in patients with atopic dermatitis. As the clinical severity of atopic dermatitis increased, the plasma IL-18 level also tended to increase. These findings suggest that IL-18 may be associated with the severity of atopic dermatitis.

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Background: It is known that the symptoms of allergic rhinitis can significantly reduce the quality of life of the patient. One of such typical symptoms of allergic rhinitis is nasal obstruction. Nasal obstruction is currently thought to be closely related to the presence and abundance of lipid mediators, such as leukotriene and thromboxane (TX) A₂. The novel drug ramatroban, a TXA₂ receptor antagonist, which has been developed by Bayer Yakuhin Ltd. (Osaka, Japan), has been demonstrated, in clinical trials, to improve nasal obstruction in the treatment of patients with allergic rhinitis and it has recently become commercially available.
Methods: In the present study, ramatroban was administered for 28 days to 10 patients who were diagnosed with perennial allergic rhinitis but were untreated. Changes in self-reported symptom scores and in vivo allergic reaction parameters were assessed during three observational periods.
Results: From baseline scores, all three symptom scores after 28 days treatment with ramatroban declined clearly in all patients, except for one patient who suffered a cold during the study period and had aggravated rhinorrhea and nasal obstruction as a result. The concentrations of histamine and TXB₂ (a metabolite of TXA₂) in the nasal fluid induced by antigen challenge after the 28 day treatment period also decreased in most subjects compared with concentrations during the pretreatment period. The symptom scores for nasal obstruction during the pretreatment period were correlated with the concentration of TXB₂ in antigen-induced nasal fluid.
Conclusions: The present study reconfirmed the clinical efficacy of a post-marketed drug, namely ramatroban, in the treatment of allergic rhinitis. In addition, the results suggest that ramatroban suppressed the secretion of chemical mediators in nasal that are thought to be involved in the allergic reaction in patients with perennial allergic rhinitis.

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Background: In addition to parvalbumin, the well-known major allergen in fish, collagen was recently identified as a new allergen in the muscle of bigeye tuna and in the skin of several species of fish. The aim of the present study was to evaluate fish muscle collagens for their reactivity with IgE in fish-allergic patients and antigenic cross-reactivity.
Methods: Collagen was purified from the white muscle of five species of fish (Japanese eel, alfonsin, mackerel, skipjack and bigeye tuna) by acid extraction and salt precipitation, whereas parvalbumin was purified from bigeye tuna by gel filtration and reverse-phase HPLC. The IgE reactivities to collagen and parvalbumin were examined by ELISA, whereas antigenic cross-reactivity among fish muscle collagens was investigated by ELISA inhibition experiments.
Results: When 15 sera from fish-allergic patients were subjected to ELISA using bigeye tuna collagen and parvalbumin, 10 sera reacted only to parvalbumin, two reacted only to collagen, two reacted to both collagen and parvalbumin and one reacted to neither collagen nor parvalbumin. The sera containing specific IgE to bigeye tuna collagen also reacted to collagens from the other four species of fish. In the ELISA inhibition experiments, bigeye tuna collagen inhibited the binding of IgE not only to bigeye tuna collagen, but also to that from the other four species of fish, suggesting cross-reactivity among the collagens from five species of fish.
Conclusions: These results demonstrate that some Japanese fish-allergic patients have specific IgE to fish muscle collagen and that fish muscle collagen is a cross-reactive allergen among various species of fish.

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Background: We previously reported that cross-linking of IgG Fc receptor II (FcγRII) induces intracellular calcium mobilization, but not histamine release in human basophils. To clarify functional activities of FcγRII on human basophils, we analyzed the FcγRII-mediated signaling events in the human basophilic leukemia cell line KU812F.
Methods: Flow cytometric methods were used to investigate the effect on intracellular calcium mobilization of cross-linking of FcγRII. KU812F cells were preincubated with anti-FcγRII monoclonal antibody (IV.3). After the addition of various concentrations of the tyrosine kinase inhibitor genistein or buffer alone, cells were stimulated with goat antimouse IgG F(ab')₂ (GAM) and analyzed with the flow cytometer. Next, in order to test the signaling events after cross-linking of FcγRII, we examined tyrosine kinase activity. The time-course of tyrosine phosphorylation after cross-linking of FcγRII and the effect of genistein on this tyrosine phosphorylation were tested by immunoblotting. Immunoprecipitation was also performed to identify the type of tyrosine kinase associated with signal transduction of FcγRII.
Results: The tyrosine kinase inhibitor genistein inhibited intracellular calcium mobilization caused by cross-linking of FcγRII in a dose-dependent manner. Rapid tyrosine phosphorylation after FcγRII cross-linking was shown by immunoblot analysis and this phosphorylation was inhibited by genistein. Furthermore, tyrosine phosphorylation of Lyn and Syk was observed upon cross-linking of FcγRII.
Conclusions: Tyrosine phosphorylation is necessary for the signaling pathway through FcγRII and tyrosine phosphorylation of Lyn and Syk, at least, is actively involved in this signal transduction.

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Background: Adenosine monophosphate (AMP) acts by releasing inflammatory mediators from mast cells and may be used for bronchial and nasal provocation tests. The aim of the present study was to determine whether AMP could be used in a dose-response manner to evaluate nasal function and to evaluate the reproducibility of nasal function measurements with nasal challenge testing using histamine and AMP in patients with perennial allergic rhinitis.
Methods: Nine patients were challenged on three separate occasions for each challenge with doubling doses of either histamine (0.25-8 mg/mL) or AMP (25-800 mg/mL). Challenge measurements were made of peak inspiratory flow rate (PIFR), acoustic rhinometry (AR) and rhinomanometry (Rhino). The provocation concentration (PC₃₀) was calculated in order to produce: (i) a 30% fall in PIFR; (ii) a 30% fall in AR and (iii) a 30% increase in nasal airway resistance in Rhino and a symptom score of 10 (of 40). The mean intrasubject coefficient of variation (CV) was calculated for baseline and the corresponding PC.
Results: Baseline CV prior to histamine were 15.1, 19.6 and 15.8 for PIFR, AR and Rhino, respectively; prior to AMP, baseline CV were 12.7, 19.6 and 10.6% for PIFR, AR and Rhino, respectively. For histamine challenge, the PC₃₀ were 26.5, 27.4 and 38.7% for PIFR, AR and Rhino, respectively. For AMP challenge, the PC₃₀ CV values were 46.2, 30.8 and 49.5% for PIFR, AR and Rhino, respectively. There was no significant difference in the provocative dose required to cause a predetermined change in response or the response at 1 mg/mL histamine and 100 mg/mL AMP.
Conclusions: Adenosine monophosphate may be used as a challenge agent for nasal challenge testing, although it results in greater variability than histamine.

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Tissue eosinophilia is often seen in Hodgkin's disease and non-Hodgkin's lymphoma of T cell lineage. It is, however, rare in non-Hodgkin's lymphoma of B cell origin. We report a case of pulmonary infiltration with eosinophilia (PIE) syndrome accompanied with non-Hodgkin's lymphoma of B cell lineage. A 42-year-old man with a long-term history of bronchial asthma consulted the local hospital due to high fever and bilateral cervical lymphadenopathy. He was diagnosed as having non-Hodgkin's lymphoma and was referred to our hospital. Marked blood eosinophilia and infiltrative shadows in both middle lung fields were recognized. After six courses of chemotherapy, including prednisolone, the shadows were ameliorated, although cervical lymphadenopathy did not show any regression, indicating refractory lymphoma. To investigate pulmonary shadows, we performed transbronchial lung biopsy and bronchoalveolar lavage (BAL) at the peak of disease activity before systemic chemotherapy. The eosinophil recruiting and activating factor interleukin (IL)-5 was undetectable in both serum and BAL fluid. Moreover, in the specimen obtained from lung biopsy, tissue eosinophilia was pathologically recognized, but IL-5 was not detected by immunohistochemical staining. These findings indicate that, in this case, any factors other than IL-5 derived from lymphoma cells may be concerned with PIE.

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Immediate hypersensitivity reactions to mannitol present naturally in pomegranate (Punica granatum) and cultivated mushroom (Agaricus bisporus) have appeared in the medical literature recently. Mannitol, being inert, cannot react with proteins to form a hapten-carrier conjugate and elicit an immune response. Therefore, it is important to understand the mechanism of immediate hypersensitivity to this sugar alcohol. A likely mechanism was conceptualized to explain how an individual can become sensitized to mannitol and how free mannitol can elicit an anaphylactic reaction in the sensitized individual. The proposed mechanism for sensitization involves the reaction of d-mannose with exposed amino groups of proteins in vivo to form Schiff base intermediates bearing a d-mannitoyl moiety, which closely resembles _D-mannitol. This intermediate appears to be responsible for eliciting the formation of mannitol-specific IgE in susceptible individuals. Once an individual is sensitized with the formation of mannitol-specific IgE, mannitol can cause anaphylactic reactions by acting either as a univalent anaphylactogen or a bivalent hapten. The Schiff base intermediate bearing the mannitoyl moiety appears to act as a true sensitizer, whereas _D-mannose appears to act as prosensitizer and _D-mannitol acts as a non-sensitizing elicitor. This hypothesis can also explain the mechanism of sensitization and IgE-mediated hypersensitivity to any sugar alcohol.

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