BACKGROUND:Grass pollen injection immunotherapy is effective in patients with summer hay fever, although efficacy must be balanced against possible side effects. The mechanism of immunotherapy is unknown but may be related to its ability to inhibit allergen-induced late responses, which are known to be characterized by infiltration of T lymphocytes, eosinophils, and cells with messenger RNA for so-called TH2-type cytokines (IL-4 and IL-5). OBJECTIVE: This study was designed to observe the effect of grass pollen immunotherapy on late nasal responses and associated cellular infiltration and cytokine mRNA expression. METHODS: We performed local nasal provocation with grass pollen (and a control challenge) in 28 patients after a 12-month double-blind, placebo-controlled trial of immunotherapy. Nasal biopsy specimens were obtained at 24 hours and processed for immunohistology and in situ hybridization studies. RESULTS:Grass pollen immunotherapy inhibited allergen-induced immediate (0 to 60 minutes) increases in sneezing (p < 0.02) and nasal blocking (p < 0.01) and late (0 to 24 hours) nasal symptoms (p < 0.05). Immunotherapy also inhibited the associated infiltration of the nasal mucosa by CD4+ T lymphocytes and total (major basic protein-containing) and "activated" (cationic protein-secreting) eosinophils (all p = 0.03). There was a significant (p = 0.04) increase in cells expressing mRNA for interferon-gamma at 24 hours after allergen challenge, which correlated inversely with patients' seasonal symptoms (r = -0.65, p < 0.05) and medication requirements (r = -0.75, p < 0.02) during the pollen season. CONCLUSION: The results suggest that successful grass pollen immunotherapy for summer hay fever may act by inhibiting allergen-induced T lymphocyte and eosinophil recruitment and eosinophil activation in the target organ, possibly through a mechanism involving protective local increases in TH1-type cells.
RCT Entities:
BACKGROUND: Grass pollen injection immunotherapy is effective in patients with summer hay fever, although efficacy must be balanced against possible side effects. The mechanism of immunotherapy is unknown but may be related to its ability to inhibit allergen-induced late responses, which are known to be characterized by infiltration of T lymphocytes, eosinophils, and cells with messenger RNA for so-called TH2-type cytokines (IL-4 and IL-5). OBJECTIVE: This study was designed to observe the effect of grass pollen immunotherapy on late nasal responses and associated cellular infiltration and cytokine mRNA expression. METHODS: We performed local nasal provocation with grass pollen (and a control challenge) in 28 patients after a 12-month double-blind, placebo-controlled trial of immunotherapy. Nasal biopsy specimens were obtained at 24 hours and processed for immunohistology and in situ hybridization studies. RESULTS: Grass pollen immunotherapy inhibited allergen-induced immediate (0 to 60 minutes) increases in sneezing (p < 0.02) and nasal blocking (p < 0.01) and late (0 to 24 hours) nasal symptoms (p < 0.05). Immunotherapy also inhibited the associated infiltration of the nasal mucosa by CD4+ T lymphocytes and total (major basic protein-containing) and "activated" (cationic protein-secreting) eosinophils (all p = 0.03). There was a significant (p = 0.04) increase in cells expressing mRNA for interferon-gamma at 24 hours after allergen challenge, which correlated inversely with patients' seasonal symptoms (r = -0.65, p < 0.05) and medication requirements (r = -0.75, p < 0.02) during the pollen season. CONCLUSION: The results suggest that successful grass pollen immunotherapy for summer hay fever may act by inhibiting allergen-induced T lymphocyte and eosinophil recruitment and eosinophil activation in the target organ, possibly through a mechanism involving protective local increases in TH1-type cells.