Immunotherapy update: mechanisms of action

Allergen immunotherapy (IT) results in reduction of symptoms of allergic rhinitis and asthma. There still is not satisfactory evidence as to the best marker that explains clinical responses. IT inhibits the early and late nasal, bronchial, and cutaneous responses to allergen challenge. There are increases in antiallergen immunoglobulin G (IgG; 2- to 10-fold) and IgG4 (10- to 100-fold), a gradual decline in antiallergen IgE antibodies, and reduced numbers of nasal or bronchial mast cells, eosinophils, and CD4+ T-helper 2 (TH2) lymphocytes. Cytokine changes include reductions in serum interleukin (IL)-4 and in vitro lymphocyte-derived IL-4 as compared with a lack of increases in interferon gamma or IL-2. In a study in which skin biopsy specimens were obtained 24 hours after intradermal grass injection, the IT-treated patients had sharply increased numbers of macrophages which had messenger RNA for IL-12. This cytokine supports development of TH0 into TH1 CD4+ lymphocytes. Allergen immunotherapy results in a profound IgG and IgA antibody response with down-regulation of TH2 and possibly up-regulation of TH1 responses.