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

Esposito S, Garziano M, Rainone V, Trabattoni D, Biasin M, Senatore L, Marchisio P, Rossi M, Principi N, Clerici M - J Transl Med (2015)

Bottom Line: 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.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.

View Article: PubMed Central - PubMed

Affiliation: Pediatric Highly Intensive Care Unit, Department of Pathophysiology and Transplantation, Università degli Studi di Milano, Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico, Via Commenda 9, 20122, Milan, Italy. susanna.esposito@unimi.it.

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.

No MeSH data available.


Related in: MedlinePlus

Percentages of pneumococcal-stimulated positive dendritic cells (CD11c+) expressing HLA-DRII (a), CD86 (b) and CD80 (c) molecules are shown at baseline and in response to therapy in children with community-acquired pneumonia (CAP) treated with antibiotics plus pidotimod and in controls treated with antibiotics only. For each analysis, 30,000 events were acquired and gated on CD11c expression and side scatter properties. Mean values + SD and statistically significant differences are indicated
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Fig1: Percentages of pneumococcal-stimulated positive dendritic cells (CD11c+) expressing HLA-DRII (a), CD86 (b) and CD80 (c) molecules are shown at baseline and in response to therapy in children with community-acquired pneumonia (CAP) treated with antibiotics plus pidotimod and in controls treated with antibiotics only. For each analysis, 30,000 events were acquired and gated on CD11c expression and side scatter properties. Mean values + SD and statistically significant differences are indicated

Mentions: The data regarding dendritic cell (DC) maturation according to treatment arm are reported in Fig. 1. DCs were characterized by analyzing the expression of surface markers associated with cell activation and maturation, MHC class II molecules (HLA-DRII) and costimulatory molecules (CD80, CD86). Cytokine production was assessed upon PBMC stimulation in vitro with pneumococcal polysaccharides or LPS. The surface and morphological activation status of DCs was comparable at baseline in both groups of subjects. The percentage of CD11c+ cells expressing either HLA-DRII (Fig. 1a), CD80 (Fig. 1b) or CD86 (Fig. 1c) significantly increased in the PDT group compared to the controls 5 and 21 days after therapy initiation. The difference in CD80 expression was also significant across time (p for trend = 0.041). Similar results were obtained upon stimulation with LPS (data not shown).Fig. 1


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

Esposito S, Garziano M, Rainone V, Trabattoni D, Biasin M, Senatore L, Marchisio P, Rossi M, Principi N, Clerici M - J Transl Med (2015)

Percentages of pneumococcal-stimulated positive dendritic cells (CD11c+) expressing HLA-DRII (a), CD86 (b) and CD80 (c) molecules are shown at baseline and in response to therapy in children with community-acquired pneumonia (CAP) treated with antibiotics plus pidotimod and in controls treated with antibiotics only. For each analysis, 30,000 events were acquired and gated on CD11c expression and side scatter properties. Mean values + SD and statistically significant differences are indicated
© Copyright Policy - OpenAccess
Related In: Results  -  Collection

License 1 - License 2
Show All Figures
getmorefigures.php?uid=PMC4559022&req=5

Fig1: Percentages of pneumococcal-stimulated positive dendritic cells (CD11c+) expressing HLA-DRII (a), CD86 (b) and CD80 (c) molecules are shown at baseline and in response to therapy in children with community-acquired pneumonia (CAP) treated with antibiotics plus pidotimod and in controls treated with antibiotics only. For each analysis, 30,000 events were acquired and gated on CD11c expression and side scatter properties. Mean values + SD and statistically significant differences are indicated
Mentions: The data regarding dendritic cell (DC) maturation according to treatment arm are reported in Fig. 1. DCs were characterized by analyzing the expression of surface markers associated with cell activation and maturation, MHC class II molecules (HLA-DRII) and costimulatory molecules (CD80, CD86). Cytokine production was assessed upon PBMC stimulation in vitro with pneumococcal polysaccharides or LPS. The surface and morphological activation status of DCs was comparable at baseline in both groups of subjects. The percentage of CD11c+ cells expressing either HLA-DRII (Fig. 1a), CD80 (Fig. 1b) or CD86 (Fig. 1c) significantly increased in the PDT group compared to the controls 5 and 21 days after therapy initiation. The difference in CD80 expression was also significant across time (p for trend = 0.041). Similar results were obtained upon stimulation with LPS (data not shown).Fig. 1

Bottom Line: 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.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.

View Article: PubMed Central - PubMed

Affiliation: Pediatric Highly Intensive Care Unit, Department of Pathophysiology and Transplantation, Università degli Studi di Milano, Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico, Via Commenda 9, 20122, Milan, Italy. susanna.esposito@unimi.it.

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.

No MeSH data available.


Related in: MedlinePlus