Venom immunotherapy modulates interleukin‐4 and interferon‐γ messenger RNA expression of peripheral T lymphocytes

Abstract

SUMMARYThe mechanism by which specific immunotherapy exerts its beneficial effect remains unclear. In order to evaluate the influence of venom immunotherapy on the T-cell cytokine pattern of allergic reactions, we studied interleukin-4 (IL-4) and interferon-g (IFN-g) mRNA expression of peripheral T lymphocytes from 12 patients undergoing rush venom desensitization, before treatment at Day 0 (D0), at Day 15 (D15) and Day 90 (D90) after treatment, and from seven controls. Antigen-specific T-cell proliferation was also determined. Cytokine mRNA expression was evaluated using in situ hybridization, 24 hr after culture of peripheral T cells with medium, venom, or an unrelated allergen. Allergen-induced T-cell proliferation decreased at D15 and D90 of rush immunotherapy (P 4 0 . 02). In venom-stimulated cultures of the patient group, there was a decrease in IL-4 mRNA-positive cells at D15 and D90 (P 4 0 . 001). Before desensitization, IFN-g mRNA expression was lower in patients than in controls and did not increase after in vitro allergen stimulation. In contrast, after immunotherapy, spontaneous IFN-g mRNA expression increased, but only at D90 (P 4 0 . 001). The cytokine pattern observed at D90 after immunotherapy was similar to that observed in control subjects. In conclusion, venom immunotherapy induced an altered cytokine mRNA pattern in allergen-stimulated T cells which was dissociated from the early changes of allergen-induced T-cell responsiveness.

IL-5 production by allergen-stimulated T cells following grass pollen immunotherapy for seasonal allergic rhinitis

“…Moreover, this study employed culture techniques that necessitated expansion of cells in IL-2 and stimulation with non-specific mitogens. Similar findings have also been reported following rush desensitization for wasp and bee venom anaphylaxis [16][17][18]. In contrast, we did not identify either a reduction in IL-5 or an increase in IFN-g production in PBMC cultures following immunotherapy, despite use of validated methods in a blinded controlled clinical study.…”

“…In support of this hypothesis, Secrist et al [13] observed a reduction in IL-4 production by allergen-specific T cell lines derived from peripheral blood of immunotherapy treated patients relative to untreated controls, and we have previously reported increased expression of IFN-g mRNA in skin and nasal biopsies of successfully treated patients after local allergen provocation [14,15]. A decrease in Th2-type and reciprocol increases in Th1-type cytokine production following high-dose antigen administration have also been described following insect venom desensitization [16][17][18]. A further feature of successful immunotherapy is a macroscopic inhibition of allergen-induced late-phase responses and an attendant reduction in the numbers of infiltrating eosinophils [15,[19][20][21].…”

IL-18 Gene Transfer by Adenovirus Prevents the Development of and Reverses Established Allergen-Induced Airway Hyperreactivity

“…These results suggest that cytokine based, allergen-specific immunotherapies with IL-18 may be effective in treating allergic diseases and asthma. Currently, conventional allergen immunotherapy, performed by the s.c. injection of increasing doses of allergen, is the only currently available therapy that alters the underlying pathologic allergen-specific Th2-driven responses, resulting in clinical tolerance to subsequent allergen exposure (10,46). Our results leads us to speculate that IL-18, in conjunction with IL-12, may serve as an effective adjuvant to enhance the efficiency of allergen-based immunotherapies, which might be effective in reversing the symptoms of asthma and allergy.…”

Mechanisms of specific immunotherapy of allergic diseases

“…However, this discrepancy could be explained by the differences in cell-culture conditions (e.g., the use of IL-4, an agent suppressing type 1 responses, in the former study. Similarly, during SIT with inhalant allergens, increased expression of IL-2 and IFN-ymRNA, as well as the presence of intracellular IFN-7 in T cells, was reported (62,65). However, other investigators could not confirm these results, and even decreased IFN-y production after house-dust-mite immunotherapy was reported (63).…”