Immunotherapy Affects the Seasonal Increase in Specific IgE and Interleukin‐4 in Serum of Patients with Seasonal Allergic Rhinitis

Abstract

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 cedar pollens were divided into a medication group and an immunotherapy group. The patients of the medication group were treated with nonsedating antihistamines alone during the pollen season. The patients of the immunotherapy group had been treated for variable periods (mean, 5.0 Ϯ 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-g (IFN-g) and soluble CD23 levels in serum. A significant increase in specific IgE and IL-4 and a significant decrease in IFN-g were observed during the pollen season in the medication group. In contrast, in the immunotherapy group, none of specific IgE, IL-4 and IFN-g 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-g 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.

Recombinant Fusion Allergens, Cry j 1 and Cry j 2 from Japanese Cedar Pollen, Conjugated with Polyethylene Glycol Potentiate the Attenuation of Cry j 1-Specific IgE Production in Cry j 1-Sensitized Mice and Japanese Cedar Pollen Allergen-Sensitized Monkeys

“…It has been reported that subcutaneous injection of conventional Japanese cedar pollen allergen reduced specific IgE and Th2 responses after more than 3 years of treatment [24]. PEG-fusion reduced specific IgE after four injections in mice and monkeys, and specific Th2 responses in mice.…”

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

“…The details and justification of the methods used in this study have been described elsewhere. 11,12 In brief, microtitration plates were coated with anti-IL-5 monoclonal antibody (MoAb) (JES1-39D10), 2 µg/ mL, and anti-IFN-␥ MoAb (ANOC 1611), 10 µg/mL, or anti-TNF-␣ MoAb (ANOC 706), 2 µg/mL, in 100 µL per well of PBS, pH 7.4. Following overnight incubation at 4°C, the wells were blocked with 1% skim milk in PBS solution for at least 1 hour at room temperature and washed 3 times with PBS containing 0.05% polysorbate 20 (washing was always performed with this buffer).…”

Ten‐Year Follow‐Up Study of Allergen‐Specific Immunoglobulin E and Immunoglobulin G4, Soluble Interleukin‐2 Receptor, Interleukin‐4, Soluble Intercellular Adhesion Molecule‐1 and Soluble Vascular Cell Adhesion Molecule‐1 in Serum of Patients on Immunotherapy for Perennial Allergic Rhinitis

“…Interleukin-4 was measured with a chemiluminescent ELISA, and the justification of the method employed in this study has been described elsewhere [10,17]. In brief, microtitre plates were coated with mouse monoclonal anti-human IL-4 antibody (R & D Systems, Minneapolis, MN, USA) and after incubation with serum samples or purified recombinant IL-4 (R & D Systems) plates were developed with biotinylated mouse anti-human IL-4 antibody (Pharmingen, San Diego, CA, USA) followed by avidine-alkaline phosphatase conjugate (Tago, Camarillo, CA, USA).…”

“…Thus, IL-4 may be the most important cytokine involved in the allergic pathogenesis, although other cytokines derived from Th2-like cells are likely to take some part in mediating allergic disorders [34,35]. Several studies have documented a significant elevation of serum IL-4 in atopic individuals compared with nonatopic controls [17,30,36]. We previously demonstrated that serum levels of IL-4 were elevated in perennial allergic rhinitis and the elevation was down-regulated by prolonged immunotherapy [17].…”

“…Several studies have documented a significant elevation of serum IL-4 in atopic individuals compared with nonatopic controls [17,30,36]. We previously demonstrated that serum levels of IL-4 were elevated in perennial allergic rhinitis and the elevation was down-regulated by prolonged immunotherapy [17]. In the present study, the levels of IL-4 at any time after initiation of immunotherapy were significantly lower than the pretreatment level and the rate of decrease in IL-4 was significantly correlated with the duration of immunotherapy, whereas IL-4 levels did not fluctuate in the untreated patients throughout the observation period.…”