Skip to main content
Top
Published in: Journal of Translational Medicine 1/2015

Open Access 01-12-2015 | Research

Immunomodulatory activity of pidotimod administered with standard antibiotic therapy in children hospitalized for community-acquired pneumonia

Authors: Susanna Esposito, Micaela Garziano, Veronica Rainone, Daria Trabattoni, Mara Biasin, Laura Senatore, Paola Marchisio, Marta Rossi, Nicola Principi, Mario Clerici

Published in: Journal of Translational Medicine | Issue 1/2015

Login to get access

Abstract

Background

Several attempts to improve immune function in young children have been made and encouraging results have been collected with pidotimod (PDT), a synthetic dipeptide molecule that seems to have immunomodulatory activity on both innate and adaptive responses. Until now, the effects of PDT on the immune system have only been studied in vivo after long-term administration to evaluate whether its immunomodulatory activity might prevent the development of infections. This study was planned to evaluate the immunomodulatory activity of PDT administered together with standard antibiotic therapy in children hospitalized for community-acquired pneumonia (CAP).

Methods

A total of 20 children hospitalized for community-acquired pneumonia (CAP) were randomized at a 1:1 ratio to receive either standard antibiotics plus pidotimod (PDT) or standard antibiotics alone to evaluate the immunomodulatory activity of PDT. Blood samples for the evaluation of immunological parameters were drawn at the time of recruitment (T0) (i.e., before therapy administration), at T3 and T5 (i.e., 3 and 5 days after the initiation of therapy) as well as at T21 (i.e., 7 days after the therapy ended).

Results

Following pneumococcal polysaccharide stimulation, the percentage of dendritic cells (DCs) expressing activation and costimulatory molecules was significantly higher in children receiving PDT plus antibiotics than in the controls. A significant increase in tumor necrosis factor-α and/or interleukin-12 secretion and expression of toll like receptor 2 was observed in PDT-treated children compared with controls; this was followed by an increased release of proinflammatory cytokines by monocytes. In the PDT-treated group, mRNA expression of antimicrobial peptides and genes involved in the inflammatory response were also augmented in comparison with the controls.

Conclusions

These results demonstrate, for the first time, that PDT administered together with standard antibiotics is associated with a favorable persistent immunomodulatory effect in children with CAP.
Literature
1.
go back to reference Principi N, Esposito S, Cavagna R, Bosis S, Droghetti R, Faelli N, et al. Recurrent respiratory tract infections in pediatric age: a population-based survey of the therapeutic role of macrolides. J Chemother. 2003;15:53–9.CrossRefPubMed Principi N, Esposito S, Cavagna R, Bosis S, Droghetti R, Faelli N, et al. Recurrent respiratory tract infections in pediatric age: a population-based survey of the therapeutic role of macrolides. J Chemother. 2003;15:53–9.CrossRefPubMed
2.
go back to reference Patria F, Longhi B, Tagliabue C, Tenconi R, Ballista P, Ricciardi G, et al. Clinical profile of recurrent community-acquired pneumonia in children. BMC Pulm Med. 2013;13:60.PubMedCentralCrossRefPubMed Patria F, Longhi B, Tagliabue C, Tenconi R, Ballista P, Ricciardi G, et al. Clinical profile of recurrent community-acquired pneumonia in children. BMC Pulm Med. 2013;13:60.PubMedCentralCrossRefPubMed
3.
go back to reference Ewing P, Otczyk DC, Occhipinti S, Kyd JM, Gleeson M, Cripps AW. Developmental profiles of mucosal immunity in pre-school children. Clin Dev Immunol. 2010;2010:196785.PubMedCentralCrossRefPubMed Ewing P, Otczyk DC, Occhipinti S, Kyd JM, Gleeson M, Cripps AW. Developmental profiles of mucosal immunity in pre-school children. Clin Dev Immunol. 2010;2010:196785.PubMedCentralCrossRefPubMed
5.
go back to reference Levy O. Innate immunity of the newborn: basic mechanisms and clinical correlates. Nat Rev Immunol. 2007;7:379–90.CrossRefPubMed Levy O. Innate immunity of the newborn: basic mechanisms and clinical correlates. Nat Rev Immunol. 2007;7:379–90.CrossRefPubMed
6.
go back to reference Vigano A, Esposito S, Arienti D, Zagliani A, Massironi E, Principi N, et al. Differential development of type 1 and type 2 cytokines and beta-chemokines in the ontogeny of healthy newborns. Biol Neonate. 1999;75:1–8.CrossRefPubMed Vigano A, Esposito S, Arienti D, Zagliani A, Massironi E, Principi N, et al. Differential development of type 1 and type 2 cytokines and beta-chemokines in the ontogeny of healthy newborns. Biol Neonate. 1999;75:1–8.CrossRefPubMed
7.
go back to reference Brodin P, Jojic V, Gao T, Bhattacharya S, Angel CJ, Furman D, et al. Variation in the human immune system is largely driven by non-heritable influences. Cell. 2015;160:37–47.CrossRefPubMed Brodin P, Jojic V, Gao T, Bhattacharya S, Angel CJ, Furman D, et al. Variation in the human immune system is largely driven by non-heritable influences. Cell. 2015;160:37–47.CrossRefPubMed
8.
go back to reference Notarangelo LD. Immunodeficiency and immune dysregulation associated with proximal defects of T cell receptor signaling. Curr Opin Immunol. 2014;31:97–101.CrossRefPubMed Notarangelo LD. Immunodeficiency and immune dysregulation associated with proximal defects of T cell receptor signaling. Curr Opin Immunol. 2014;31:97–101.CrossRefPubMed
9.
go back to reference Tomlinson G, Chimalapati S, Pollard T, Lapp T, Cohen J, Camberlein E, et al. TLR-mediated inflammatory responses to Streptococcus pneumoniae are highly dependent on surface expression of bacterial lipoproteins. J Immunol. 2014;193:3736–45.PubMedCentralCrossRefPubMed Tomlinson G, Chimalapati S, Pollard T, Lapp T, Cohen J, Camberlein E, et al. TLR-mediated inflammatory responses to Streptococcus pneumoniae are highly dependent on surface expression of bacterial lipoproteins. J Immunol. 2014;193:3736–45.PubMedCentralCrossRefPubMed
10.
go back to reference Labuda LA, de Jong SE, Meurs L, Amoah AS, Mbow M, Ateba-Ngoa U, et al. Differences in innate cytokine responses between European and African children. PLoS One. 2014;9:e95241.PubMedCentralCrossRefPubMed Labuda LA, de Jong SE, Meurs L, Amoah AS, Mbow M, Ateba-Ngoa U, et al. Differences in innate cytokine responses between European and African children. PLoS One. 2014;9:e95241.PubMedCentralCrossRefPubMed
12.
go back to reference Vareille M, Kieninger E, Edwards MR, Regamey N. The airway epithelium: soldier in the fight against respiratory viruses. Clin Microbiol Rev. 2011;24:210–29.PubMedCentralCrossRefPubMed Vareille M, Kieninger E, Edwards MR, Regamey N. The airway epithelium: soldier in the fight against respiratory viruses. Clin Microbiol Rev. 2011;24:210–29.PubMedCentralCrossRefPubMed
13.
go back to reference Heier I, Malmstrom K, Sajantila A, Lohi J, Makela M, Jahnsen FL. Characterisation of bronchus-associated lymphoid tissue and antigen-presenting cells in central airway mucosa of children. Thorax. 2011;66:151–6.CrossRefPubMed Heier I, Malmstrom K, Sajantila A, Lohi J, Makela M, Jahnsen FL. Characterisation of bronchus-associated lymphoid tissue and antigen-presenting cells in central airway mucosa of children. Thorax. 2011;66:151–6.CrossRefPubMed
14.
go back to reference Heier I, Malmstrom K, Pelkonen AS, Malmberg LP, Kajosaari M, Turpeinen M, et al. Bronchial response pattern of antigen presenting cells and regulatory T cells in children less than 2 years of age. Thorax. 2008;63:703–9.CrossRefPubMed Heier I, Malmstrom K, Pelkonen AS, Malmberg LP, Kajosaari M, Turpeinen M, et al. Bronchial response pattern of antigen presenting cells and regulatory T cells in children less than 2 years of age. Thorax. 2008;63:703–9.CrossRefPubMed
15.
go back to reference Esposito S, Musio A. Immunostimulants and prevention of recurrent respiratory tract infections. J Biol Regul Homeost Agents. 2013;27:627–36.PubMed Esposito S, Musio A. Immunostimulants and prevention of recurrent respiratory tract infections. J Biol Regul Homeost Agents. 2013;27:627–36.PubMed
16.
go back to reference Feleszko W, Ruszczyński M, Zalewski BM. Non-specific immune stimulation in respiratory tract infections. Separating the wheat from the chaff. Paediatr Respir Rev. 2014;15:200–6.PubMed Feleszko W, Ruszczyński M, Zalewski BM. Non-specific immune stimulation in respiratory tract infections. Separating the wheat from the chaff. Paediatr Respir Rev. 2014;15:200–6.PubMed
17.
go back to reference Esposito S, Castellazzi L, Garbarino F. Can probiotic administration during pregnancy and the first year of life effectively reduce the risk of infections and allergic diseases in childhood? J Biol Regul Homeost Agents. 2014;28:565–73.PubMed Esposito S, Castellazzi L, Garbarino F. Can probiotic administration during pregnancy and the first year of life effectively reduce the risk of infections and allergic diseases in childhood? J Biol Regul Homeost Agents. 2014;28:565–73.PubMed
18.
go back to reference Auteri A, Pasqui AL, Bruni F, Saletti M, Di Renzo M, Bova G. Effect of pidotimod, a new immunostimulating agent, on some aspects of immune response. In vitro study. Pharmacol Res. 1992;26:196–7.CrossRefPubMed Auteri A, Pasqui AL, Bruni F, Saletti M, Di Renzo M, Bova G. Effect of pidotimod, a new immunostimulating agent, on some aspects of immune response. In vitro study. Pharmacol Res. 1992;26:196–7.CrossRefPubMed
19.
go back to reference Migliorati G, D’Adamio L, Coppi G, Nicoletti I, Riccardi C. Pidotimod stimulates natural killer cell activity and inhibits thymocyte cell death. Immunopharmacol Immunotoxicol. 1992;14:737–48.CrossRefPubMed Migliorati G, D’Adamio L, Coppi G, Nicoletti I, Riccardi C. Pidotimod stimulates natural killer cell activity and inhibits thymocyte cell death. Immunopharmacol Immunotoxicol. 1992;14:737–48.CrossRefPubMed
20.
go back to reference Carta S, Silvestri M, Rossi GA. Modulation of airway epithelial cell functions by pidotimod: NF-kB cytoplasmatic expression and its nuclear translocation are associated with an increased TLR-2 expression. Ital J Pediatr. 2013;39:29.PubMedCentralCrossRefPubMed Carta S, Silvestri M, Rossi GA. Modulation of airway epithelial cell functions by pidotimod: NF-kB cytoplasmatic expression and its nuclear translocation are associated with an increased TLR-2 expression. Ital J Pediatr. 2013;39:29.PubMedCentralCrossRefPubMed
21.
go back to reference Namazova-Baranova LS, Alekseeva AA, Kharit SM, Kozhevnikova TN, Taranushenko TE, Tuzankina IA, et al. Efficacy and safety of pidotimod in the prevention of recurrent respiratory infections in children: a multicentre study. Int J Immunopathol Pharmacol. 2014;27:413–9.PubMed Namazova-Baranova LS, Alekseeva AA, Kharit SM, Kozhevnikova TN, Taranushenko TE, Tuzankina IA, et al. Efficacy and safety of pidotimod in the prevention of recurrent respiratory infections in children: a multicentre study. Int J Immunopathol Pharmacol. 2014;27:413–9.PubMed
22.
go back to reference Licari A, De Amici M, Nigrisoli S, Marseglia A, Caimmi S, Artusio L, et al. Pidotimod may prevent recurrent respiratory infections in children. Minerva Pediatr. 2014;66:363–7.PubMed Licari A, De Amici M, Nigrisoli S, Marseglia A, Caimmi S, Artusio L, et al. Pidotimod may prevent recurrent respiratory infections in children. Minerva Pediatr. 2014;66:363–7.PubMed
23.
go back to reference Zuccotti GV, Mameli C, Trabattoni D, Beretta S, Biasin M, Guazzarotti L, et al. Immunomodulating activity of pidotimod in children with down syndrome. J Biol Regul Homeost Agents. 2013;27:253–8.PubMed Zuccotti GV, Mameli C, Trabattoni D, Beretta S, Biasin M, Guazzarotti L, et al. Immunomodulating activity of pidotimod in children with down syndrome. J Biol Regul Homeost Agents. 2013;27:253–8.PubMed
24.
go back to reference Tan TQ, Mason EO Jr, Wald ER, Barson WJ, Schutze GE, Bradley JS, et al. Clinical characteristics of children with complicated pneumonia caused by Streptococcus pneumoniae. Pediatrics. 2002;110:1–6.CrossRefPubMed Tan TQ, Mason EO Jr, Wald ER, Barson WJ, Schutze GE, Bradley JS, et al. Clinical characteristics of children with complicated pneumonia caused by Streptococcus pneumoniae. Pediatrics. 2002;110:1–6.CrossRefPubMed
25.
go back to reference Principi N, Esposito S. Management of severe community-acquired pneumonia of children in developing and developed countries. Thorax. 2011;66:815–22.CrossRefPubMed Principi N, Esposito S. Management of severe community-acquired pneumonia of children in developing and developed countries. Thorax. 2011;66:815–22.CrossRefPubMed
26.
go back to reference World Health Organization, Pneumonia Vaccine Trial Investigators’ Group. Standardization of interpretation of chest radiographs for the diagnosis of pneumonia in children. WHO/V&B/01.35. Geneva: World Health Organization; 2001. World Health Organization, Pneumonia Vaccine Trial Investigators’ Group. Standardization of interpretation of chest radiographs for the diagnosis of pneumonia in children. WHO/V&B/01.35. Geneva: World Health Organization; 2001.
27.
go back to reference Esposito S, Indinnimeo L, Duse M, Giancane G, Battistini E, Longhi R, et al. Diagnosis and treatment of community-acquired pneumonia in pediatric age-guidelines of the Italian Pediatric Societies (SIP, SITIP, SIMRI, SIAIP, SIPPS, SIMEUP). Minerva Pediatr. 2009;61:887–90.PubMed Esposito S, Indinnimeo L, Duse M, Giancane G, Battistini E, Longhi R, et al. Diagnosis and treatment of community-acquired pneumonia in pediatric age-guidelines of the Italian Pediatric Societies (SIP, SITIP, SIMRI, SIAIP, SIPPS, SIMEUP). Minerva Pediatr. 2009;61:887–90.PubMed
28.
go back to reference Dalod M, Chelbi R, Malissen B, Lawrence T. Dendritic cell maturation: functional specialization through signaling specificity and transcriptional programming. EMBO J. 2014;33:1104–16.PubMedCentralCrossRefPubMed Dalod M, Chelbi R, Malissen B, Lawrence T. Dendritic cell maturation: functional specialization through signaling specificity and transcriptional programming. EMBO J. 2014;33:1104–16.PubMedCentralCrossRefPubMed
29.
go back to reference Merad M, Sathe P, Helft J, Miller J, Mortha A. The dendritic cell lineage: ontogeny and function of dendritic cells and their subsets in the steady state and the inflamed setting. Annu Rev Immunol. 2013;31:563–604.CrossRefPubMed Merad M, Sathe P, Helft J, Miller J, Mortha A. The dendritic cell lineage: ontogeny and function of dendritic cells and their subsets in the steady state and the inflamed setting. Annu Rev Immunol. 2013;31:563–604.CrossRefPubMed
30.
go back to reference Kim CH, Kim DJ, Lee SJ, Jeong YJ, Kang MJ, Lee JY, et al. Toll-like receptor 2 promotes bacterial clearance during the initial stage of pulmonary infection with Acinetobacter baumannii. Mol Med Rep. 2014;9:1410–4.PubMed Kim CH, Kim DJ, Lee SJ, Jeong YJ, Kang MJ, Lee JY, et al. Toll-like receptor 2 promotes bacterial clearance during the initial stage of pulmonary infection with Acinetobacter baumannii. Mol Med Rep. 2014;9:1410–4.PubMed
31.
go back to reference Wiesner J, Vilcinskas A. Antimicrobial peptides: the ancient arm of the human immune system. Virulence. 2010;1:440–64.CrossRefPubMed Wiesner J, Vilcinskas A. Antimicrobial peptides: the ancient arm of the human immune system. Virulence. 2010;1:440–64.CrossRefPubMed
32.
go back to reference Guaní-Guerra E, Santos-Mendoza T, Lugo-Reyes SO, Terán LM. Antimicrobial peptides: general overview and clinical implications in human health and disease. Clin Immunol. 2010;135:1–11.CrossRefPubMed Guaní-Guerra E, Santos-Mendoza T, Lugo-Reyes SO, Terán LM. Antimicrobial peptides: general overview and clinical implications in human health and disease. Clin Immunol. 2010;135:1–11.CrossRefPubMed
33.
go back to reference Al-Rayahi IA, Sanyi RH. The overlapping roles of antimicrobial peptides and complement in recruitment and activation of tumor-associated inflammatory cells. Front Immunol. 2015;6:2.PubMedCentralCrossRefPubMed Al-Rayahi IA, Sanyi RH. The overlapping roles of antimicrobial peptides and complement in recruitment and activation of tumor-associated inflammatory cells. Front Immunol. 2015;6:2.PubMedCentralCrossRefPubMed
Metadata
Title
Immunomodulatory activity of pidotimod administered with standard antibiotic therapy in children hospitalized for community-acquired pneumonia
Authors
Susanna Esposito
Micaela Garziano
Veronica Rainone
Daria Trabattoni
Mara Biasin
Laura Senatore
Paola Marchisio
Marta Rossi
Nicola Principi
Mario Clerici
Publication date
01-12-2015
Publisher
BioMed Central
Published in
Journal of Translational Medicine / Issue 1/2015
Electronic ISSN: 1479-5876
DOI
https://doi.org/10.1186/s12967-015-0649-z

Other articles of this Issue 1/2015

Journal of Translational Medicine 1/2015 Go to the issue
Obesity Clinical Trial Summary

At a glance: The STEP trials

A round-up of the STEP phase 3 clinical trials evaluating semaglutide for weight loss in people with overweight or obesity.

Developed by: Springer Medicine

Highlights from the ACC 2024 Congress

Year in Review: Pediatric cardiology

Watch Dr. Anne Marie Valente present the last year's highlights in pediatric and congenital heart disease in the official ACC.24 Year in Review session.

Year in Review: Pulmonary vascular disease

The last year's highlights in pulmonary vascular disease are presented by Dr. Jane Leopold in this official video from ACC.24.

Year in Review: Valvular heart disease

Watch Prof. William Zoghbi present the last year's highlights in valvular heart disease from the official ACC.24 Year in Review session.

Year in Review: Heart failure and cardiomyopathies

Watch this official video from ACC.24. Dr. Biykem Bozkurt discusses last year's major advances in heart failure and cardiomyopathies.