The immunomodulatory molecule pidotimod induces the expression of the NOD-like receptor NLRP12 and attenuates TLR-induced inflammation.

Pidotimod (3-L-pyroglutamyl-L-thiaziolidine-4-carboxylic acid) (PDT) is a synthetic dipeptide with in vitro and in vivo immunomodulatory properties that is largely used for treatment and prevention of infections in paediatric and disease-prone patients. However, the effects of PDT on cellular immune responses are still poorly characterized and there is little information on the mechanism of action of this compound. It has been speculated that PDT action may be exerted through the interaction with a Pattern Recognition Receptor (PRR). Therefore, to gain a further understanding of the immune pathways involved by PDT, we first decided to investigate whether PDT could modify the immune response triggered by TLR ligands. Monocytic cells were exposed to PDT then stimulated with a panel of TLR agonists. Under these experimental conditions, we observed a significant decrease in the synthesis of key proinflammatory mediators in comparison to the production observed in TLR-stimulated cells that were not treated with PDT. Using RT² Profiler PCR Array we have observed that PDT specifically up-regulates the expression of the NOD-like receptor NLRP12 mRNA in the absence of any further costimulation. Increase of NLRP12 in cells treated with PDT was confirmed using specifically designed real-time quantitative PCR and western blotting assays where a clear increase in the amount of NLRP12 protein was detected. Furthermore, in myeloid/monocytic cells we demonstrated that PDT treatment counteracts the NLRP12 reduction induced by TLR agonists. Finally, the results obtained using NLRP12 silenced cells showed that down-regulation of the proinflammatory function occurring in PDT-treated cells upon interaction with TLRs is associated with the increased levels of NLRP12 induced by PDT. To our knowledge this is the first evidence of an immunomodulatory peptide that upregulates NLRP12 and, through this molecule, antagonizes the TLR-induced inflammatory response. These results pave the way for the development of innovative therapeutic approaches aimed at controlling different pathological settings such as tumorigenesis, systemic inflammatory processes and autoimmunity, where NLRP12 plays a crucial role.

Susceptibility to varicella-zoster among pregnant women in the province of Lecce, Italy.

BACKGROUND: Varicella is predominantly a childhood disease, considered a mild self-limiting disease that can have serious complications for a pregnant woman and her developing fetus. OBJECTIVES: We investigated the susceptibility to varicella-zoster Virus (VZV) among pregnant women in the province of Lecce. STUDY DESIGN: A cross-sectional study was carried out in Departments of Gynecology and Obstetrics of the Province of Lecce, where 539 pregnant women were recruited, and face-to-face interviews were conducted. Varicella IgG tests were performed. RESULTS: The prevalence of varicella susceptibility among pregnant mothers was 10.6%. The prevalence of IgG antibodies increases significantly with increasing age, from 62.5% in the age group 15-19 years to 94.4% in the age group 40-49 years. DISCUSSION: In the Italian National Vaccination Plan 2005-2007, varicella vaccine is only recommended for childbearing women. A safe and effective vaccine is available and no abnormalities have been observed among infants born to susceptible women who received varicella vaccines during pregnancy. Such a high number of susceptible women indicates that preventive and informative programs should be introduced, even among those who do not plan to become pregnant. Routine counselling, varicella IgG antibody screening and varicella vaccination should be considered if they have no history of the infection, to reduce the risk of fetal complications and the cost of healthcare associated with the infection.