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Published in: Clinical and Molecular Allergy 1/2015

Open Access 01-12-2015 | Review

Pidotimod: the state of art

Authors: Beatrice E Ferrario, Silvia Garuti, Fulvio Braido, Giorgio W Canonica

Published in: Clinical and Molecular Allergy | Issue 1/2015

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Abstract

Despite the use of antibiotics and vaccines, the frequency of respiratory tract infections is still high and these infections interest a wide range of patients, from children to aged people, including in particular these extreme categories because of the deficiency of their immune system, due to immaturity in the former case and to “immunosenescence” in the latter. For that reason immunostimulant drugs are getting more important to prevent and to attenuate infections. Pidotimod (3-L-pyroglutamyl-L-thiazolidine-4carboxylic acid) is a synthetic dipeptide with immunomodulatory properties. We reviewed studies conducted on different categories of patients, with particular attention on children and senile patients suffering from recurrent respiratory tract infections, associated, or not, with asthma or COPD. The outcomes considered are both clinical and laboratory parameters. The common end-point of these studies is that Pidotimod has an immunomodulatory activity which is able both to improve the clinical conditions of patients and to enhance and stimulate their immunity cells (lymphocytes but not only) functions acting on adaptive and innate immunity. Pidotimod is also able to increase the concentration of salivary IgA directed against bacteria; furthermore, it can modulate airway epithelial cells functions up-regulating the expression of toll-like receptors and acting on adhesion molecules. According to studies conducted on patients with atopic asthma, it seems that Pidotimod could affect T-lymphocytes balance with a possible addictional anti-allergic activity. Furthermore, it has been demonstrated an improvement of FEV1 and PEF in asthmatic patients treated with Pidotimod. Main clinical outcomes are the reduction of the number of infectious episodes, lesser severity of signs and symptoms and, consequently, a reduction in use of antibiotics and symptomatic drugs, less working and school days lost, less mortality and morbidity. The studies considered give positive results, confirming Pidotimod’s efficacy. Furthermore, many studies show a good safety profile of the drug, without recording serious adverse events and mutagenic potential, and a very low incidence of side effects. Pidotimod is also a more safe solution in patients subjected to vaccination, if compared to lyophilized polibacterial, which can’t be administered for thirty days before vaccination.
Literature
1.
go back to reference Zuccotti GV, Mameli C. Pidotimod: the past and the present. Int J Ped. 2013;39(75):2–3. Zuccotti GV, Mameli C. Pidotimod: the past and the present. Int J Ped. 2013;39(75):2–3.
3.
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. 2013;27(1):207–12. 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. 2013;27(1):207–12.
4.
go back to reference Schwarze J, Mackenzie KJ. Novel insights into immune and inflammatory responses to respiratory viruses. Thorax. 2013;68:108–10.CrossRefPubMed Schwarze J, Mackenzie KJ. Novel insights into immune and inflammatory responses to respiratory viruses. Thorax. 2013;68:108–10.CrossRefPubMed
5.
go back to reference Giagulli C, Noerder M, Avolio M, Becker PD, Fiorentini S, Guzman CA, et al. Pidotimod promotes functional maturation of dendritic cells and display adjuvant properties at the nasal mucosa level. Int Immunopharmacol. 2009;9:1366–73.CrossRefPubMed Giagulli C, Noerder M, Avolio M, Becker PD, Fiorentini S, Guzman CA, et al. Pidotimod promotes functional maturation of dendritic cells and display adjuvant properties at the nasal mucosa level. Int Immunopharmacol. 2009;9:1366–73.CrossRefPubMed
6.
go back to reference Rossi GA, Peri C, Raynal ME, Defilippi A-C, Risso FM, Schenone G, et al. Naturally occurring immune response against bacteria commonly involved in upper respiratory tract infections: analysis of the antigen-specific salivary IgA levels. Immunol Lett. 2003;2003(86):85–91.CrossRef Rossi GA, Peri C, Raynal ME, Defilippi A-C, Risso FM, Schenone G, et al. Naturally occurring immune response against bacteria commonly involved in upper respiratory tract infections: analysis of the antigen-specific salivary IgA levels. Immunol Lett. 2003;2003(86):85–91.CrossRef
7.
go back to reference Wu S, Jiang ZY, Sun YF, Yu B, Chen J, Dai CQ, et al. Microbiota regulates the TLR7 signaling pathway against respiratory tract influenza A virus infection. Curr Microbiol. 2013;67(4):414–22.CrossRefPubMed Wu S, Jiang ZY, Sun YF, Yu B, Chen J, Dai CQ, et al. Microbiota regulates the TLR7 signaling pathway against respiratory tract influenza A virus infection. Curr Microbiol. 2013;67(4):414–22.CrossRefPubMed
8.
go back to reference Carta S, Silvestri M, Rossi G. Modulation of airway epithelial cell functions by Pidotimod: NF-kB cytoplasmatic expression and its nuclear translocation are associated with an increased TLR-2 expression. It J Ped. 2013;39(29):2–9. Carta S, Silvestri M, Rossi G. Modulation of airway epithelial cell functions by Pidotimod: NF-kB cytoplasmatic expression and its nuclear translocation are associated with an increased TLR-2 expression. It J Ped. 2013;39(29):2–9.
9.
go back to reference Fogli M, Caccuri F, Iaria ML, Giagulli C, Corbellini S, Campilongo F, Caruso A, Fiorentini S. The immunomodulatory molecule Pidotimod induces the expression of the NOD-like receptor NLRP12 and attenuates TLR-induced inflammation. Studio Clinico 2014. Fogli M, Caccuri F, Iaria ML, Giagulli C, Corbellini S, Campilongo F, Caruso A, Fiorentini S. The immunomodulatory molecule Pidotimod induces the expression of the NOD-like receptor NLRP12 and attenuates TLR-induced inflammation. Studio Clinico 2014.
10.
go back to reference Zhou Y, Dai Y. Comparison of effects of Pidotimod and spleen aminopeptide on clinical symptoms and Th1/Th2 cytokines in children with RRI. Chin J Bioch Pharm. 2012;33(1):64–9. Zhou Y, Dai Y. Comparison of effects of Pidotimod and spleen aminopeptide on clinical symptoms and Th1/Th2 cytokines in children with RRI. Chin J Bioch Pharm. 2012;33(1):64–9.
11.
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(5):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(5):363–7.PubMed
12.
go back to reference La Mantia I, Grillo C, Mattina T, Zaccone P, Xiang M, Di Mauro M, et al. Prophylaxis with the novel immunomodulator Pidotimod reduces the frequency and severity of upper respiratory tract infections in children with Down’s Syndrome. J Chemother. 1999;11(2):126–30.CrossRefPubMed La Mantia I, Grillo C, Mattina T, Zaccone P, Xiang M, Di Mauro M, et al. Prophylaxis with the novel immunomodulator Pidotimod reduces the frequency and severity of upper respiratory tract infections in children with Down’s Syndrome. J Chemother. 1999;11(2):126–30.CrossRefPubMed
13.
go back to reference Yan Y. Changes of immune function in children with refractory mycoplasma pneumoniae pneumonia and effects of Pidotimod. J Clin Pediatr. 2008;26(7):570–2. Yan Y. Changes of immune function in children with refractory mycoplasma pneumoniae pneumonia and effects of Pidotimod. J Clin Pediatr. 2008;26(7):570–2.
14.
go back to reference Gourgiotis D, Papadopoulos NG, Bossios A, Zamanis P, Saxoni-Papageorgiou P. Immune modulator Pidotimod decreases the in vitro expression of CD30 in peripheral blood mononuclear cells of atopic asthmatic and normal children. J Asthma. 2004;41(3):285–7.CrossRefPubMed Gourgiotis D, Papadopoulos NG, Bossios A, Zamanis P, Saxoni-Papageorgiou P. Immune modulator Pidotimod decreases the in vitro expression of CD30 in peripheral blood mononuclear cells of atopic asthmatic and normal children. J Asthma. 2004;41(3):285–7.CrossRefPubMed
15.
go back to reference Zhigui J, Jiang Z, Liang H, Yang C, Li W, Lin Y. Effect of Pidotimod in preventing the relapse of Henoch-Schonlein purpura and the impact on immune function. Chin Med Herl J 2012; 9 (18). Zhigui J, Jiang Z, Liang H, Yang C, Li W, Lin Y. Effect of Pidotimod in preventing the relapse of Henoch-Schonlein purpura and the impact on immune function. Chin Med Herl J 2012; 9 (18).
16.
go back to reference Zheng H, Sheng W. The observation of Pidotimod in preventing the relapse of nephrotic syndrome in 86 cases. Drugs and clinical studies 2009. Zheng H, Sheng W. The observation of Pidotimod in preventing the relapse of nephrotic syndrome in 86 cases. Drugs and clinical studies 2009.
17.
go back to reference Di F, Di Filippo S, Varacalli S, Zardo F. Pidotimod nel trattamento delle faringotonsilliti recidivanti. Actamed Drug Rev Spec. 1995;192(96):1–8. Di F, Di Filippo S, Varacalli S, Zardo F. Pidotimod nel trattamento delle faringotonsilliti recidivanti. Actamed Drug Rev Spec. 1995;192(96):1–8.
18.
go back to reference Li X, Bai H. Treatment of 30 cases of senile pneumonia with Pidotimod. Clin Pharm 2004; 13 (9). Li X, Bai H. Treatment of 30 cases of senile pneumonia with Pidotimod. Clin Pharm 2004; 13 (9).
19.
go back to reference Borghi MO, Fain C, Barcellini W, Del Papa N, La Rosa L, Nicoletti F, et al. Ex vivo effect of Pidotimod on peripheral blood mononuclear cell immune funtions: study of an elderly population. Int J Immunother. 1994;X(1):35–9. Borghi MO, Fain C, Barcellini W, Del Papa N, La Rosa L, Nicoletti F, et al. Ex vivo effect of Pidotimod on peripheral blood mononuclear cell immune funtions: study of an elderly population. Int J Immunother. 1994;X(1):35–9.
20.
go back to reference Lin D, Xu B. Impact of Pidotimod on local immunity in the genital tract of female patients with non-gonococcal urethritis. Chin J Clin. 2013;7(8):3585–6. Lin D, Xu B. Impact of Pidotimod on local immunity in the genital tract of female patients with non-gonococcal urethritis. Chin J Clin. 2013;7(8):3585–6.
21.
go back to reference Li Y, Dai Y, Deng B, Liang X, Xie Z, Chen H. Effect of Pidotimod on interleukin-13 of patients with recurrent genital herpes. J Hain Med Univ. 2011;17(8):1068–71. Li Y, Dai Y, Deng B, Liang X, Xie Z, Chen H. Effect of Pidotimod on interleukin-13 of patients with recurrent genital herpes. J Hain Med Univ. 2011;17(8):1068–71.
22.
go back to reference Zhang C, Zhang W, Lin H. Effect of Pidotimod on expressions of IL-2 and IL-10 of patients with genital herpes and curative effect observation. Clin J Pharmacoepidemiol. 2010;19(3):126–31. Zhang C, Zhang W, Lin H. Effect of Pidotimod on expressions of IL-2 and IL-10 of patients with genital herpes and curative effect observation. Clin J Pharmacoepidemiol. 2010;19(3):126–31.
23.
go back to reference Zhang J, Li Y. Efficacy of ceftriaxone combined with Pidotimod on serofast syphilis. Acta Ac Med Qing Univ 2011; 47 (1). Zhang J, Li Y. Efficacy of ceftriaxone combined with Pidotimod on serofast syphilis. Acta Ac Med Qing Univ 2011; 47 (1).
24.
go back to reference Guerra B, Perino A, Polatti F, Scala M. Pidotimod in the managemente of vulvar papillomatosis: double-blind clinical trial versus placebo. Am J Ther. 1998;5:147–52.CrossRefPubMed Guerra B, Perino A, Polatti F, Scala M. Pidotimod in the managemente of vulvar papillomatosis: double-blind clinical trial versus placebo. Am J Ther. 1998;5:147–52.CrossRefPubMed
25.
go back to reference Zervoudis S, Iatrakis G, Peitsidis P, Peitsidou A, Papandonopolos L, Nikolopoulou MK, et al. Complementary treatment with oral Pidotimod plus vitamin C after laser vaporization for female geniital warts: a prospective study. J Med Life. 2010;3(3):286–8.PubMedPubMedCentral Zervoudis S, Iatrakis G, Peitsidis P, Peitsidou A, Papandonopolos L, Nikolopoulou MK, et al. Complementary treatment with oral Pidotimod plus vitamin C after laser vaporization for female geniital warts: a prospective study. J Med Life. 2010;3(3):286–8.PubMedPubMedCentral
26.
go back to reference Li Y, Cai H, Gu Y, Li Y. Effects of Pidotimod on immune function of patients with chronic hepatitis C. J Lanz Univ 2006; 32 (1). Li Y, Cai H, Gu Y, Li Y. Effects of Pidotimod on immune function of patients with chronic hepatitis C. J Lanz Univ 2006; 32 (1).
27.
go back to reference Holt P. Prevention - What is the most promising approach? Ped All Immunol. 2014;25:12–4.CrossRef Holt P. Prevention - What is the most promising approach? Ped All Immunol. 2014;25:12–4.CrossRef
28.
go back to reference Wu Y, Ling J. Observation of impact and efficay of Pidotimod on serum interleukin-4 and gamma-interferon levels in children with asthma. Chin Med Herl J. 2013;10(24):101–5. Wu Y, Ling J. Observation of impact and efficay of Pidotimod on serum interleukin-4 and gamma-interferon levels in children with asthma. Chin Med Herl J. 2013;10(24):101–5.
29.
go back to reference Jackson DJ, Hartert TV, Martinez FD, Weiss ST, Fahy JV. Asthma: NHLBI workshop oh the primary prevention of chronic lung diseases. Ann ATS. 2014;11(3):139–45.CrossRef Jackson DJ, Hartert TV, Martinez FD, Weiss ST, Fahy JV. Asthma: NHLBI workshop oh the primary prevention of chronic lung diseases. Ann ATS. 2014;11(3):139–45.CrossRef
30.
go back to reference Zhai F, Liu X. The effect of Pidotimod in the prevention and Treatment of Pediatric Bronchial Asthma. Chin J Biochem Pharm. 2011;32(2):151–5. Zhai F, Liu X. The effect of Pidotimod in the prevention and Treatment of Pediatric Bronchial Asthma. Chin J Biochem Pharm. 2011;32(2):151–5.
31.
go back to reference Ma X, Sun X. The effect of Pidotimod on serum IL-4, IFN-gamma and IgE in asthmatic children. Chin J Biochem Pharm. 2011;32(5):400–3. Ma X, Sun X. The effect of Pidotimod on serum IL-4, IFN-gamma and IgE in asthmatic children. Chin J Biochem Pharm. 2011;32(5):400–3.
32.
go back to reference Bisetti G, Ciappi G, Bariffi F, Catena E, Rocco V, Vaccaro L, et al. Evaluation of the efficacy of Pidotimod on the exacerbations in patients affected with chronic bronchitis. Arzneim Forsch Drug Res. 1994;44 II(12):1499–502. Bisetti G, Ciappi G, Bariffi F, Catena E, Rocco V, Vaccaro L, et al. Evaluation of the efficacy of Pidotimod on the exacerbations in patients affected with chronic bronchitis. Arzneim Forsch Drug Res. 1994;44 II(12):1499–502.
33.
go back to reference Ciaccia A et al. Pidotimod activity against chronic bronchitis exacerbations. Arzneim Forsch Drug Res. 1994;44(II):1516–20. Ciaccia A et al. Pidotimod activity against chronic bronchitis exacerbations. Arzneim Forsch Drug Res. 1994;44(II):1516–20.
34.
go back to reference Benetti GP, Illeni MT, Passera A, Bombelli G, Lavecchia G, Uslenghi C. Ex vivo evaluation of Pidotimod activity in patients with chronic obstructive pulmonary disease. Arneim Forsch Drug Res. 1994;44 II(12):1503–5. Benetti GP, Illeni MT, Passera A, Bombelli G, Lavecchia G, Uslenghi C. Ex vivo evaluation of Pidotimod activity in patients with chronic obstructive pulmonary disease. Arneim Forsch Drug Res. 1994;44 II(12):1503–5.
35.
go back to reference Chen J, Wang H, Liu Y, Xia C, Qi M. Immunological function of T-lynphocyte in the elderly with chronic obstuctive pulmonary disease during acute exacerbations medication intervention. Chin J Geriatr. 2006;25(6):434–40. Chen J, Wang H, Liu Y, Xia C, Qi M. Immunological function of T-lynphocyte in the elderly with chronic obstuctive pulmonary disease during acute exacerbations medication intervention. Chin J Geriatr. 2006;25(6):434–40.
36.
go back to reference Cogo R. Valutazione sperimentale controllata dell’attività di Pidotimod in pazienti affetti da BPCO. Min Pneumol. 2014;53:1–6. Cogo R. Valutazione sperimentale controllata dell’attività di Pidotimod in pazienti affetti da BPCO. Min Pneumol. 2014;53:1–6.
37.
go back to reference Pozzi E, Dolcetti A, Orlandi O, Cirianni C, Moreo G, Piacenza G, et al. Pidotimod in the treatment in patients affected by bacterial exacerbations of chronic bronchitis. Arzneim Forsch Drug Res. 1994;44(II):1495–8. Pozzi E, Dolcetti A, Orlandi O, Cirianni C, Moreo G, Piacenza G, et al. Pidotimod in the treatment in patients affected by bacterial exacerbations of chronic bronchitis. Arzneim Forsch Drug Res. 1994;44(II):1495–8.
38.
go back to reference Cogo R, Ramponi A, Monzani G, Uslenghi C, Girardello R. Valutazione dell’attività del Pidotimod sulla secrezione di IgA in pazienti affetti da BPCO. Giorn It Allergol Immunol Clin. 1993;3:253–9. Cogo R, Ramponi A, Monzani G, Uslenghi C, Girardello R. Valutazione dell’attività del Pidotimod sulla secrezione di IgA in pazienti affetti da BPCO. Giorn It Allergol Immunol Clin. 1993;3:253–9.
39.
go back to reference Mailland F, Coppi G, Silingardi S. Pharmacokinetics and oral bioavailability of Pidotimod in humans. Arzneim Forsch Drug Res. 1994;44(II):1465–9. Mailland F, Coppi G, Silingardi S. Pharmacokinetics and oral bioavailability of Pidotimod in humans. Arzneim Forsch Drug Res. 1994;44(II):1465–9.
40.
go back to reference Qi X, Wang L, Zhu J. Water in oil in water double emulsions: an excellent delivey system for improving the oral bioavailability of Pidotimod in rats. J Pharmaceut Sci May. 2011;100(6):2203–11.CrossRef Qi X, Wang L, Zhu J. Water in oil in water double emulsions: an excellent delivey system for improving the oral bioavailability of Pidotimod in rats. J Pharmaceut Sci May. 2011;100(6):2203–11.CrossRef
41.
go back to reference Adams K, Allen JA, Brooker PC, Henderson L, Jones E, Proudlock RJ, et al. Genotoxicity testing of Pidotimod in vivo and in vitro. Arzneim Forsch Drug Res. 1994;44 II(12):1454–9. Adams K, Allen JA, Brooker PC, Henderson L, Jones E, Proudlock RJ, et al. Genotoxicity testing of Pidotimod in vivo and in vitro. Arzneim Forsch Drug Res. 1994;44 II(12):1454–9.
Metadata
Title
Pidotimod: the state of art
Authors
Beatrice E Ferrario
Silvia Garuti
Fulvio Braido
Giorgio W Canonica
Publication date
01-12-2015
Publisher
BioMed Central
Published in
Clinical and Molecular Allergy / Issue 1/2015
Electronic ISSN: 1476-7961
DOI
https://doi.org/10.1186/s12948-015-0012-1

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