Noma T

Induction of allergen-specific IL-2 responsiveness of lymphocytes after respiratory syncytial virus infection and prediction of onset of recurrent wheezing and bronchial asthma.

BACKGROUND In pediatric patients with bronchial asthma and/or atopic dermatitis, peripheral lymphocytes are activated if they are stimulated with the responsible antigen, resulting in induction of responsiveness to IL-2. Because some nursing infants experience recurrent wheezing after respiratory syncytial virus (RSV) infection, attention is being directed to progression of the disease to bronchial asthma. OBJECTIVE The study was designed to elucidate the mechanism of the onset of allergic diseases after RSV infection. METHODS We examined allergen-specific IL-2 responsiveness induced in lymphocytes in the peripheral blood of infants after infection by RSV. The relationship between the onset of recurrent wheezing and antigen-specific IL-2 responsiveness was analyzed in 25 pediatric patients who could be followed up for 3 years after RSV infection. RESULTS Stimulation of lymphocytes with ovalbumin, alpha-casein, and mite (Dermatophagoides farinae) antigens induced significantly higher responsiveness to IL-2 in the RSV-infected infant group than in the healthy infant and disease control groups of the same age. There was no clear correlation between the IgE RAST scores for D. farinae, ovalbumin, and alpha-casein and IL-2 responsiveness. The families of RSV-infected infants had a high incidence of history of allergy (67%), but there was no significant difference in the incidence of patients with positive test results for IL-2 responsiveness between the groups with and without a familial history of allergy. The D. farinae-specific IL-2 responsiveness was significantly increased in the group with the symptom (16 patients) for a value of 1.64 +/- 0.13 (mean +/- SEM) compared with the value of 1.31 +/- 0.21 in the asymptomatic group (9 patients). The incidence of patients with positive test results for IL-2 responsiveness was 68.8% in the symptomatic group and 44.4% in the asymptomatic group. Similarly, the ovalbumin-specific IL-2 responsiveness was significantly increased in the symptomatic group (1.63 +/- 0.17) compared with the asymptomatic group (1.12 +/- 0.26). The incidence of patients with positive test results was 62.5% and 22.2%, respectively. alpha-Casein-specific IL-2 responsiveness was also higher in the symptomatic group than in the asymptomatic group, but the difference was not statistically significant. In the patient groups without RSV infection, on the other hand, the D. farinae-, ovalbumin-, and alpha-casein-specific IL-2 responsiveness in the symptomatic group were all similar to that in the asymptomatic group; no significant increases were detected. CONCLUSION The results indicated that after RSV infection, lymphocytes acquire specific susceptibility to D. farinae, a mite antigen, and food antigens, particularly ovalbumin. Hence, it is thought that positive IL-2 responsiveness specific for D. farinae and/or ovalbumin, detected several months after RSV infection, can be a prediction factor for the onset of allergic diseases, such as recurrent wheezing and bronchial asthma.

Cytokine production in children outgrowing hen egg allergy

Background Approximately 40 to 80% of egg‐allergic children outgrow egg allergy after 2 to 5 years.

Pattern of cytokine production by T cells from adolescents with asthma in remission after stimulation with dermatophagoides farinae antigen

ABSTRACT: Children with asthma usually become asymptomatic by the time they reach age 20 y. To clarify the immunologic mechanisms responsible for this phenomenon, we studied patients in remission and others who still had frequent asthma attacks. Patients were grouped by clinical status, and three variables were measured: serum levels of lgE, production of 11.4 and interferon (IFN)-γ, and the activation of T cells induced by Dermaophagoides farinae (DF) antigen. Df-induced activation of T cells (as measured by antigen-induced 11.2 responsiveness) or 11.2 synthesis itself was induced in patients with active asthma but not in normal subjects. These responses were much weaker in patients in remission. When stimulated by Df antigen in vitro, lymphocytes from patients with active asthma produced much more 11.4 than did the cells from normal subjects, and cells from patients in remission produced only a small amount. In contrast, under similar conditions lymphocytes from patients with active asthma produced less IFN-γ than did the cells from normal subjects. Production of IFN-γ stimulated by Df antigen was high in patients in remission but not in normal subjects. Thus, up-regulated IFN-γ production after exposure to Df antigen might reduce 11.4 secretion, which would suppress IgE production and would improve clinical status. Df antigen may suppress Df-induced allergic responses in patients with asthma in remission.

A comparative investigation of the restorative effects of roxithromycin on neutrophil activities

The effects of roxithromycin, a macrolide antibiotic, on neutrophil activities were investigated in six seriously handicapped patients with severe mental retardation. Neutrophil activities were evaluated by flow cytometry using a heparinized blood analysis method. All six patients showed decreased levels of neutrophil phagocytosis, intracellular killing, and CD11b expression. Treatment with roxithromycin in vitro selectively restored the decreased phagocytic and bactericidal activities of neutrophils in these patients. There was no significant restorative effect with cefaclor, ofloxacin, or aztreonam. These results suggest the need to consider therapeutic effects of antibiotics on neutrophil functions in patients at increased risk for bacterial infections due to decreased neutrophil activities.

Fetal growth promotion in allergic children

Several in vitro studies have suggested the presence of Th2‐skewed immunity during pregnancy in infants with atopic diseases. Our study indicated that allergic infants showed a higher birth weight and shorter gestational period at birth than those of non‐allergic peers. Moreover, allergic mothers gave birth to neonates whose birth weights and gestational ages were higher and shorter than those of the non‐allergic mothers, respectively. Thus, our data clearly demonstrated the promotion of intrauterine growth, either in the allergic children, or allergic mothers. Such an intrauterine environment favorable for the fetal growth may also accelerate the development of allergic diseases in their offspring that are most probably caused by the Th2‐oriented immunity.

Effect of oxatomide on T-cell activation and the production of interferon-γ in mite sensitive asthma

Interleukin-2 responsiveness of lymphocytes induced by Dermatophagoides farinae antigen was suppressed upon exposure to 20 to 2000 ng/ml of oxatomide for 24 h in a dose-related manner in children with mite-sensitive bronchial asthma. Suppression was greater in the plastic-adherent antigen-presenting cells than in the T-cells. Oxatomide suppressed the production of interleukin-1alpha induced by Dermatophagoides farinae antigen in plastic-adherent cells. These results indicate that the target cells of oxatomide are antigen-presenting cells and not T-cells. Oxatomide also suppressed interleukin-2 responsiveness in lymphocytes exposed to purified protein derivative, but not in those exposed to concanavalin A. Unlike its effect on cell proliferation, oxatomide potentiated the Dermatophagoides farinae-induced production of interferon-gamma, which was suppressed by stimulation with Dermatophagoides farinae antigen in lymphocytes from the patients. In contrast, production of interferon-gamma induced by concanavalin A was not affected by this drug. These results indicate that oxatomide suppresses interleukin-2 responsiveness of allergen-activated helper T-cells and increases the production of interferon-gamma induced by Dermatophagoides farinae antigen, without causing cell proliferation.

IL-12 affects Dermatophagoides farinae–induced IL-4 production by T cells from pediatric patients with mite-sensitive asthma

BACKGROUND IL-12 is a critical cytokine in the regulation of immune responses produced by phagocytic cells exposed to microorganism infection. OBJECTIVE We sought to study the effect of low doses and high doses of IL-12 on TH1 versus TH2 cytokine expression to elucidate the etiology of mite antigen-sensitive bronchial asthma in infants. METHODS We studied the effect of IL-12 on Dermatophagoides farinae (Df) antigen-induced IL-4 production and subsequent production of IgE by PBMCs from pediatric patients with asthma. RESULTS Simultaneous addition of 1 to 10 ng/mL IL-12 to cultures enhanced Df-induced IL-4 production, although low doses (0.05 to 0.1 ng/mL) of IL-12 downregulated IL-4 production. Endogenous IL-12 is required for such production. These phenomena were not observed in Df-stimulated control PBMCs. In contrast, on stimulation with the same dose of Df, IFN-gamma production by patient PBMCs was enhanced in a dose-dependent fashion by addition of IL-12. Quantification analysis of RT-PCR-amplified DNA fragments by laser-induced fluorescence showed that a high dose of IL-12 augments mRNA expression for IL-4 protein synthesis, whereas a low dose of IL-12 inhibits IL-4 mRNA expression, and that the signal of mRNA for IFN-gamma protein synthesis was increased on Df stimulation in a dose-dependent fashion. Df-induced in vitro production of IgE and Df-specific IgE in serum from severe combined immunodeficient mice reconstituted with PBMCs were increased by treatment with high doses of IL-12, whereas low doses of IL-12 inhibited that production. The combined results indicate that at a low dose of IL-12, IL-4 and IFN-gamma production was regulated reciprocally; however, at high doses of IL-12, cells produced IL-4 and IFN-gamma simultaneously, and neither cytokine was regulated. CONCLUSION Low-dose and high-dose IL-12 induce TH1 responses, and high-dose IL-12 induces both TH1 responses and TH2 or TH0 responses. Consequently, the IL-4 production may overcome TH1-type cell activation of IgE production in patients with mite-sensitive bronchial asthma.

Inhibition by lecithin-bound iodine (LBI) of inducible allergen-specific T lymphocytes' responses in allergic diseases

In atopic patients, allergen-sensitized T lymphocytes specifically proliferate in the presence of T cell-growth factor, interleukin 2 (IL-2). Lecithin-bound iodine (LBI), which has been used as a therapeutic modality for patients with bronchial asthma (BA), effectively inhibited Dermatophagoides farinae (Df) mite antigen-induced IL-2 responsiveness in concentrations comparable to LBI concentrations in blood. IL-2-responding T cells were more sensitive to LBI than antigen-presenting cells, whereas LBI suppressed the release of interleukin 1 (IL-1) elicited by Df antigen. In addition, ovalbumin (OVA)-induced IL-2 responsiveness in egg sensitive patients and purified protein-derivative (PPD)-induced IL-2 responsiveness were similarly inhibited by LBI. The IL-2 responsiveness induced by concanavalin A (Con A), however, was not changed. On the basis of these results, LBI may act as a slight immunosuppressant to inhibit the induction of allergen-specific lymphocytes and to improve the clinical status in allergic diseases.

Reduced IL-1 production in adolescents with mite antigen asthma in remission

To determine the immunological mechanisms associated with outgrowing mite antigen‐induced bronchial asthma during adolescence, we studied the relationship between clinical status and Dermatophagoides farinae (Df) antigen‐induced peripheral cell activation by measuring IL‐1α and IL‐lβ production in patients with bronchial asthma. After antigen‐driven restimulation in vitro, there was increased IL‐1α, IL‐1β production by peripheral blood mononuclear cells (PBMC) from patients with active bronchial asthma, while cellular IL‐1α, IL‐1β production was reduced in patients with asthma in remission. IL‐1α and IL‐1β production by PBMC (possibly reflecting airway inflammation) after exposure to Df antigen might be down‐regulated in patients outgrowing mite antigen‐induced asthma, because lipopolysaccharide‐induced IL‐1α, IL‐1β production (seen in both normal individuals and patients with active asthma) was also reduced when patients were in remission.

Food allergy and anaphylaxis – 2055: Slow specific oral tolerance induction in children with hen’s egg allergy. 3-days on / 4 days off schedule

Methods Seven children aged 9 months to 6.6 years (median 1.7 years) with hen’s egg allergy were performed open oral food challenge tests with boiled hen’s egg to define the threshold dose. Subjects underwent SOTI in which they intake boiled hen’s egg at home 3 days every week. The dose was increased every 1 to 2 weeks from approximately one fourth of the threshold dose to 60g. Clinical response and immunologic changes before and after SOTI were evaluated.