Pidotimod: A Reappraisal

Abstract

Pidotimod (Polimod ®) is a synthetic dipeptide molecule with biological and immunological activity on both the adaptive and the innate immune responses. In vitro studies, both from animal and human specimens, have documented a good activity on innate and adaptive immune responses and have been confirmed by in vivo studies. These activities have been applied in clinical studies demonstrating the efficacy of pidotimod in reducing the rate of recurrent infections of the upper respiratory and urinary tracts in children. The same results were obtained in recurrent respiratory tract infections in adults. Interestingly, these effects are more evident in the setting of immune defects such as senescence, Down's syndrome, and cancer.Pidotimod (Polimod ®) is a synthetic dipeptide molecule with biological and immunological activity on both the adaptive and the innate immune responses (Fig. 1). In comparison with biological response modifiers of extractive origin, the synthetic process ensures a high purity product with a high reproducibility among batches. Pidotimod is rapidly absorbed by the gastrointestinal tract with a bioavailability of 45%. The plasma half life is 4 h with poor metabolism and renal elimination of the unmodified molecule.In vitro studies from both animal and human specimens have documented a good activity on innate and adaptive immune responses and have been confirmed by in vivo studies. These activities have been applied in clinical studies demonstrating the efficacy of pidotimod in reducing the rate of recurrent infections of the upper respiratory and urinary tract in children. The same results were obtained in recurrent respiratory tract infections in adults. More importantly, these effects are more evident in the setting of immune defects such as senescence, Down's syndrome, and cancer. The aim of this review is to analyze the effects of pidotimod on the innate and adaptive immunity and the studies of clinical efficacy. Animal studiesThe first experiments were designed to demonstrate a protective effect of pidotimod in experimental infections in mice. Mice injected intraperitoneally (i.p.) with P. mirabilis, P. vulgaris, S. aureus, K. pneumoniae or P. aeruginosa are protected from death when treated concomitantly with repeated injections ofpidotimod. The protective effect reached a 100% survival with Proteus strains, 90% with S. aureus and 40% with more aggressive bacteria such as Pseudomonas and Klebsiella strains. This effect is dose-dependent and can be strengthened by a synergistic activity with beta-lactam antibiotics

Synergistic effect of methionine encephalin (MENK) combined with pidotimod(PTD) on the maturation of murine dendritic cells (DCs)

“…15,16 In vitro studies, both from animals and human specimens, have documented good activity on innate and adaptive immune responses, and have been confirmed by in vivo studies. The previous studies also demonstrated that PTD itself did not have antibacterial activity, but when combined with antibacterial agents could be effective in improving clinical symptoms of patients, promoting recovery and shortening hospital stay.…”

“…So it is crucial to understand the regulation of DC maturation to gain further insight into their in vivo function. [21][22][23][24][25] Both MENK and PTD are peptide molecules of TH1 modulatiors, 5,16 and each of these peptides, when used separately, promotes functional maturation of dendritic cells and have a marked effect on suppressing the progression of some tumors. 26,27 Whether these two peptides exert synergistic effect on DCs remains unclear so far.…”

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“…Interestingly, these effects are more evident in the setting of immune defects such as senescence, downs syndrome, and cancer. Researches have also demonstrated that pidotimod itself does not have antibacterial activity, but when combined with antibacterial agents, pidotimod can be effective in improving clinical effects, promoting recovery, and shortening therapy time 6,7,8 .…”

Pidotimod: the past and the present

“…Pidotimod (3-L-pyroglutamyl-L-thiaziolidine-4carboxylic acid) is a synthetic dipeptide molecule with immunomodulatory properties [14]. It is a highly purified molecule with high reproducibility among batches.…”