No abstract

Grass pollen immunotherapy is effective, although efficacy must be balanced against side-effects. In a double-blind, placebo-controlled trial of 40 adult patients with summer hay fever, immunotherapy with a depot grass pollen extract (Phleum pratense, Alutard SQ) reduced symptoms and medication requirements with an acceptable minimal level of side-effects (31). The original placebo group, as well as the actively treated group, have now received active immunotherapy in an open fashion for a further 3 years. An important question was whether continued injection treatment was accompanied by maintained clinical improvement. By analysis of diary symptoms, rescue medication, and visual analogue scores during the pollen season, we show that efficacy was maintained throughout the 3-4-year study period. Clinical improvement was accompanied by a sustained and marked decrease in immediate conjunctival allergen sensitivity and a further significant decrease in the size of the allergen-induced late cutaneous response. In contrast, an initial decrease in the allergen-induced immediate cutaneous response was not maintained at 3-4 years. Of the patients, 37/40 completed the first year, 33/40 the second year, and 32/40 the third year of treatment. Patients dropped out for reasons other than the outcome of immunotherapy. During a total of 2598 injections, five immediate systemic reactions were observed, all during the induction (not maintenance) phase, and all occurred within 10 min of injection and responded promptly to adrenaline. Grass pollen immunotherapy is effective and safe, provided it is performed on carefully selected patients by trained physicians with immediate access to resuscitative measures.

Specific allergen immunotherapy (SIT) to date is the only treatment shown to have long-term benefit in patients with IgE-mediated allergic disorders such as allergic rhinitis. In seasonal rhinitis and asthma, and to a lesser extent in perennial allergic rhinitis, SIT is highly effective in reducing symptoms and medication use in patients who fail to respond adequately to usual pharmacologic treatments and these effects are maintained for at least three years after discontinuation [1][2][3][4][5][6]. Clinical outcomes such as early and late skin, nasal and bronchial reactions have been shown to decrease after treatment. For example, immunotherapy results in a reduction in immediate allergen-induced symptoms and the concentrations of inflammatory mediators in nasal lavage fluid, including histamine and prostaglandin D 2 [7]. The risk/benefit of SIT is less favourable in patients with chronic asthma because of an increased risk of developing IgE-mediated systemic side-effects and, rarely, anaphylaxis. Therefore, delineation of the immunological mechanisms underlying successful immunotherapy, with a view to develop more targeted forms of therapy with maintained efficacy but reduced risk of side-effects, remains an important goal.While the clinical efficacy of SIT is well-documented, the molecular mechanisms are incompletely understood. Current evidence suggests that specific immunotherapy exerts an effect on several aspects of the immune system, including modulation of allergen-specific B cell as well as T cell responses. Studies on the effect of immunotherapy have demonstrated reduced basophil reactivity to allergens [8], reductions in mucosal recruitment of inflammatory cells [9], deviation of Th2 cytokine responses to allergens in favour of Th1 responses [10,[11][12][13] and the induction of IL-10 producing regulatory T cells [14][15][16]. In addition, changes in serum antibody titres in response to immunotherapy have been described, mostly as increases in allergen-specific IgG antibodies, particularly the IgG4 isotype [17,[18][19][20][21][22], sometimes accompanied by blunting of seasonal increases in IgE antibodies.In order to improve safety while maintaining efficacy, attempts have been made to reduce allergen-induced IgE responses during the course of immunotherapy. For example, one therapeutic approach has been the use of novel vaccine adjuvants based on bacterial lipopolysaccharide (LPS). LPS is a bacterial membrane component specific to Gram-negative bacteria, which acts as an immunomodulator by activating the innate immune response. LPS consists of a complex glycolipid composed of a hydrophilic polysaccharide portion and a hydrophobic domain known as lipid A, which contains the adjuvant activity of LPS [23]. The clinical use of LPS is limited because of toxicity, including possible induction of a sepsis-like systemic inflammatory response syndrome. Chemical modifications of LPS have been developed such as a detoxified version of the lipid A moiety of Salmonella minnesota R595 termed monophosphoryl lipid A ...

This is an open access article under the terms of the Creat ive Commo ns Attri bution-NonCo mmercial License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited and is not used for commercial purposes.