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RESEARCH ARTICLE
Immunomodulator Clarithromycin Enhances Mucosal and Systemic Immune Responses and Reduces Re-Infection Rate in Pediatric Patients with Influenza Treated with Antiviral Neuraminidase Inhibitors: A Retrospective Analysis
- Wakako Shinahara,
- Etsuhisa Takahashi,
- Takako Sawabuchi,
- Masaru Arai,
- Nobuo Hirotsu,
- Yoshio Takasaki,
- Shizuo Shindo,
- Kyoko Shibao,
- Takashi Yokoyama,
- Kiyoshi Nishikawa,
- Masahiro Mino,
- Minako Iwaya,
- Yuji Yamashita,
- [ ... ],
- Hiroshi Kido mail
- , [ view all ]
Abstract
Background/Aims
Treatment with antiviral neuraminidase inhibitors suppresses influenza viral replication and antigen production, resulting in marked attenuation of mucosal immunity and mild suppression of systemic immunity in mice. This study investigated the effects of immunomodulator clarithromycin (CAM) supplementation on mucosal and systemic immunity in pediatric patients with influenza treated with neuraminidase inhibitors.Methods
A retrospective, non-randomized case series study was conducted among five treatment groups of 195 children aged 5.9±3.3 years infected with influenza A in 2008/2009 season. The five treatment groups were oseltamivir (OSV), zanamivir (ZNV), OSV+CAM, ZNV+CAM and untreated groups. Anti-viral secretory IgA (S-IgA) levels in nasal washes and IgG levels in sera were measured. The re-infection rate was analyzed among the same five treatment groups in the 2009/2010 season.Results
Treatment of influenza with OSV and ZNV for 5 days attenuated the induction of anti-viral S-IgA in nasal washes and anti-viral IgG in serum, compared with the untreated group. The combination of CAM plus OSV or ZNV boosted and restored the production of mucosal S-IgA and systemic IgG. The re-infection rates in the subsequent season were significantly higher in the OSV and ZNV groups than the untreated, while CAM+OSV and CAM+ZNV tended to reduce such rate.Conclusions
CAM restored the attenuated anti-viral mucosal and systemic immunity and reduced the re-infection rate in the subsequent year in pediatric patients with influenza treated with OSV and ZNV.Citation: Shinahara W, Takahashi E, Sawabuchi T, Arai M, Hirotsu N, et al. (2013) Immunomodulator Clarithromycin Enhances Mucosal and Systemic Immune Responses and Reduces Re-Infection Rate in Pediatric Patients with Influenza Treated with Antiviral Neuraminidase Inhibitors: A Retrospective Analysis. PLoS ONE 8(7): e70060. doi:10.1371/journal.pone.0070060Editor: Dennis W. Metzger, Albany Medical College, United States of AmericaReceived: February 17, 2013; Accepted: June 17, 2013; Published: July 17, 2013Copyright: © 2013 Shinahara et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.Funding: This study was supported in part by a Grant in-Aid (21249061), the Special Coordination Funds for Promoting Science and Technology of Ministry of Education, Culture, Sports, Science and Technology of Japan and SENTAN Japan Science and Technology Agency. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.Competing interests: The authors have declared that no competing interests exist.
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