The mechanism of a pullulan-conjugated antigen immunotherapy for japanese cedar pollenosis

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A pullulan-conjugated antigen (CS-560) has been developed to reduce the adverse effect and to enhance the effect for the Japanese cedar-specific Immunotherapy (IT). If the mechanism of IT can be fully elucidated and the treatment can be conducted safely and with specificity, IT should be reconsidered as a superior treatment for JC-pollenosis. Thirteen patients with JC-pollenosis who had received IT were compared to 10 patients without IT. All patients were followed through 2 pollen seasons with allergy diaries. Peripheral blood mononuclear cells (PBMC) were collected before IT and just before the pollen seasons, and those were stimulated with pollen extract. The concentration of Interleukin (IL)-4, IL-5 and IFN-gamma in the culture supernatants were determined using enzyme-linked immunosorbent assay. According to the allergy dairies, we confirmed the clinical efficacy of CS-560. The symptom medication scores were significantly decreased by IT. The level of IL-4 and IL-5 declined only in the IT group. However, the level of IFN-gamma did not change in both groups. Specific-IT for JC-pollenosis using CS-560 clearly modified cytokine production by PBMC. After that, we have observed Japanese cedar pollinosis patients who had taken by 18-months immunotherapy using pullulan-conjugated antigen for four consecutive years. We have carefully examined some clinical factors including the evaluation by symptom medication score and patients' personal evaluations. These factors seemed to be positively correlated. Neither the change in serum specific-IgE nor the change in serum specific-IgG4 was related to clinical efficacy. Our results suggested that the change in the production of IL-4 and IL-5 from mononuclear cells stimulated by antigen in vitro would be a good indicator of the efficacy of immunotherapy.