-Original-

Serum Cytokine Interactions Are Implicated in the Mechanism of Action of Sublingual Immunotherapy for Japanese Cedar Pollinosis

Kenichi Shimada¹, Minoru Gotoh¹, Kimihiro Okubo¹, Takachika Hiroi², Osamu Kaminuma² and Akihiro Nakaya^3,4

¹Department of Otorhinolaryngology, Nippon Medical School, Tokyo, Japan
²Tokyo Metropolitan Bureau of Social Welfare and Public Health, Tokyo, Japan
³Department of Allergy and Immunology, Tokyo Metropolitan Institute of Medical Sciences, Tokyo, Japan
⁴Osaka University, Osaka, Japan

Objective: This study aimed to investigate whether interactions between multiple serum cytokines may be implicated in the mechanism of action (MOA) of sublingual immunotherapy (SLIT) for Japanese cedar pollinosis.
Methods: A Tokyo Metropolitan Bureau of Social Welfare and Public Health-initiated clinical study of active SLIT involving 202 patients with Japanese cedar pollinosis was jointly conducted by Tokyo Metropolitan Institute of Medical Science and Nippon Medical School between 2006 and 2008. Fifty target cytokines were quantified in serum samples collected at 6 times from baseline to the end of the study, for 300 cytokine measurements in total, using Bio-Plex Pro Human Cytokine Group I/II Panels. Therapeutic outcome was assessed based on nasal symptom scores and quality-of-life questionnaire results.
Results: Fifty-five percent of patients were free of symptoms or reported symptomatic improvements by 2 grades or greater after 2 years of SLIT treatment, while 27% showed no improvement or worsening of symptoms. Thirty-eight patients who benefited the most from treatment (responders) as well as 37 patients who benefited the least from treatment (non-responders) were identified and their serum cytokine profiles were compared. Cluster analysis of the 300 cytokine measurements identified 6 cytokine clusters that were strongly correlated with a positive response to treatment, and this correlation was consistent throughout the treatment.
Conclusion: Certain cytokine clusters are strongly correlated with a positive therapeutic outcome, suggesting they have a role in the MOA of immunotherapy.

J Nippon Med Sch 2018; 85: 250-258

Keywords
serum cytokines, sublingual immunotherapy, cluster analysis

Correspondence to
Kenichi Shimada, MD, Department of Otorhinolaryngology, Nippon Medical School, 1-1-5 Sendagi, Bunkyo-ku, Tokyo 113-8603, Japan
shimaken8733@wit.ocn.ne.jp

Received, December 14, 2017
Accepted, March 20, 2018