Immunomodulatory activity of pidotimod administered with standard antibiotic therapy in children hospitalized for community-acquired pneumonia.
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.
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.
Susanna
S
Esposito
Immunology Unit, Department of Biomedical and Clinical Sciences, Luigi Sacco Hospital, Università degli Studi di Milano, Milan, Italy. micaela.garziano@unimi.it.
Micaela
M
Garziano
Immunology Unit, Department of Biomedical and Clinical Sciences, Luigi Sacco Hospital, Università degli Studi di Milano, Milan, Italy. veronica.rainone@unimi.it.
Veronica
V
Rainone
Immunology Unit, Department of Biomedical and Clinical Sciences, Luigi Sacco Hospital, Università degli Studi di Milano, Milan, Italy. daria.trabattoni@unimi.it.
Daria
D
Trabattoni
Immunology Unit, Department of Biomedical and Clinical Sciences, Luigi Sacco Hospital, Università degli Studi di Milano, Milan, Italy. mara.biasin@unimi.it.
Mara
M
Biasin
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. lausen88@hotmail.it.
Laura
L
Senatore
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. paola.marchisio@unimi.it.
Paola
P
Marchisio
Department of Clinical Sciences and Community Health, Università degli Studi di Milano, Milan, Italy. marta.rossi@unimi.it.
Marta
M
Rossi
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. nicola.principi@unimi.it.
Nicola
N
Principi
Department of Physiopathology and Transplantation, Università degli Studi di Milano, Milan, Italy. mario.clerici@unimi.it.|Don C. Gnocchi Foundation IRCCS, Milan, Italy. mario.clerici@unimi.it.
Mario
M
Clerici
D000276:Adjuvants, Immunologic / Q000008:administration & dosage* / Q000627:therapeutic use; D000293:Adolescent; D000900:Anti-Bacterial Agents / Q000008:administration & dosage* / Q000627:therapeutic use; D002648:Child; D002675:Child, Preschool; D017714:Community-Acquired Infections / Q000188:drug therapy*; D003713:Dendritic Cells / Q000276:immunology / Q000378:metabolism; D005260:Female; D006760:Hospitalization; D006801:Humans; D007113:Immunity, Innate; D007249:Inflammation; D018664:Interleukin-12 / Q000378:metabolism; D008297:Male; D010455:Peptides / Q000737:chemistry; D011014:Pneumonia / Q000188:drug therapy*; D011135:Polysaccharides, Bacterial / Q000737:chemistry; D011761:Pyrrolidonecarboxylic Acid / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000627:therapeutic use; D012333:RNA, Messenger / Q000378:metabolism; D012141:Respiratory Tract Infections / Q000188:drug therapy; D053778:Thiazolidines / Q000008:administration & dosage* / Q000627:therapeutic use; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism
D000276:Adjuvants, Immunologic; D000900:Anti-Bacterial Agents; D010455:Peptides; D011135:Polysaccharides, Bacterial; D012333:RNA, Messenger; D053778:Thiazolidines; D014409:Tumor Necrosis Factor-alpha; D018664:Interleukin-12; C064893:pidotimod; D011761:Pyrrolidonecarboxylic Acid