Production of interleukin-12 by monocytes and interferon-gamma by natural killer cells in allergic patients during rush immunotherapy.

BACKGROUND: Allergen specific immunotherapy modifies the immunologic response to allergen exposure; however, the role of cells composing the innate immune system, such as monocytes and natural killer (NK) cells, in this mechanism is still unclear. OBJECTIVE: To examine the effect of rush immunotherapy (RIT) on early allergen-induced cytokine production by peripheral blood mononuclear cells from treated cat- and birch-allergic patients. METHODS: Twelve allergic patients received RIT, and another 4 served as controls. Blood samples were taken before the start and after 3 days, 1 week, 3 weeks, and 3 months of RIT. Allergen-induced production of interleukin-12 (IL-12) by monocytes and interferon-gamma (IFN-gamma) by NK cells was evaluated by means of flow cytometry. RESULTS: Before the start of RIT, allergic patients had significantly lower numbers of IL-12+ monocytes compared with healthy subjects (P = .01). The percentage of IL-12+ monocytes increased after 3 months of RIT (P = .003). In the allergic control group, the proportion of IL-12+ monocytes evaluated after 3 months was not different from baseline and was significantly lower compared with that in the RIT group (P = .005). Before treatment, the percentage of IFN-gamma+ NK cells was lower in allergic patients than in healthy subjects (P = .04). The percentage of IFN-gamma+ NK cells increased after 3 weeks (P = .03) and 3 months (P = .01) of RIT. CONCLUSIONS: Restoration of the cytokine imbalance by immunotherapy is not only restricted to the cells of the adaptive immune system but also concerns cells composing the innate immune system.

Basophil interleukin 4 and interleukin 13 production is suppressed during the early phase of rush immunotherapy.

BACKGROUND: Studies using rush immunotherapy (RIT) have shown that rapid protection can be achieved using protocols allowing a fast increment of allergen dose. We examined the early effects of RIT on basophil numbers and expression of CD203c, production of interleukin (IL)-4 and IL-13 and histamine release by basophils in the peripheral blood of patients treated with immunotherapy and controls. METHODS: Twelve patients treated with RIT and 4 untreated controls were included in the study. Any adverse events were evaluated during the incremental phase of RIT. Mononuclear cells were isolated before the start of RIT and 3 days, 1 week, 4 weeks and 3 months after the beginning of the treatment. Histamine release upon allergen stimulation, expression of CD203c and allergen-induced production of IL-4 and IL-13 by basophils were examined. RESULTS: Significant decreases in blood basophil count (p = 0.02) were observed early in the treatment, returning to baseline values 1 week after the start of RIT. Similarly, histamine release decreased at day 3 (p = 0.02), but returned to pretreatment levels after 1 week. Also, the percentage of IL-4+ and IL-13+ basophils and levels of CD203c expression were markedly reduced early in the treatment. IL-4 and IL-13 production correlated with histamine release and CD203c expression. Histamine release and production of IL-4 and IL-13 by basophils before the treatment correlated with the severity of adverse events during the incremental phase of RIT. CONCLUSION: We report the decrease in blood basophil numbers, their lower activation status and the reduced production of IL-4 and IL-13 early in the course of RIT. This early suppression of basophil activation could be one mechanism behind the protective effect of RIT.

The effect of omalizumab on nasal allergic inflammation.

BACKGROUND: In sensitized patients, coupling between IgE and FcepsilonRI receptors on mast cells leads to release of proinflammatory mediators and a subsequent influx of inflammatory cells to the affected organ. Omalizumab (Xolair; formerly rhuMAb-E25) binds to circulating IgE, thus preventing induction of the allergic process. OBJECTIVE: We investigated the effect of treatment with omalizumab on seasonal allergic rhinitis and related changes in inflammatory cell numbers in nasal biopsy specimens. METHODS: Patients were randomized to treatment with omalizumab or placebo before the pollen season; the treatment was started and continued during season. Symptoms and use of medication were recorded, and blood samples and nasal biopsy specimens were obtained before and during season. Immunocytochemistry was performed on biopsy sections through use of the following antibodies: anti-CD4, CD8 (T lymphocytes), EG2, and anti-eosinophil peroxidase (eosinophils), anti-tryptase (mast cells), human neutrophil lipocalin (neutrophils), and antibodies against IgE and FcepsilonRI. RESULTS: During the season, blood eosinophils increased in placebo-treated patients but not in omalizumab-treated patients (P =.01); the difference between the treatment groups was significant (P =.04). Free IgE in serum decreased significantly (P =.0002) in omalizumab-treated patients but not in placebo-treated patients; the difference between the groups was significant (P =.0001). In nasal biopsy specimens, the number of eosinophil peroxidase-positive staining cells increased in the placebo-treated patients (P =.003) but not in the actively treated patients during the season; the difference between the groups was significant (P =.0001). The number of IgE(+) staining cells decreased significantly in the omalizumab group during the season in comparison with the placebo group (P =.04). CONCLUSION: The clinical benefit of treatment with omalizumab is associated with an anti-inflammatory effect on cellular markers in blood and nasal tissue.