Neonatal tolerization

Grabie N. Karin N Expansion of neonatal tolerance to self in adult life. II. Tolerance preferentially spreads in an intramolecular manner. Int Immunol 1999 11 907-913. 

Neonatal tolerance induction in rodents Option of dosing animals very early in life to produce animals tolerant to subsequent chronic administration of human proteins (potential to conduct rodent bioassay) Use of clinical product No data on positive controls Limited if any data on biopharmaceuticals... 

Table4. Comparison between regulatory T-cell induced during neonatal tolerance to a drug and those responsible for the resistance to drug re-challenge.

Field AC, Bloch MF, Bellon B Neonatal tolerance to a Th2-medlated autoimmune disease generates CD8-i-Tc1 regulatory cells. J Autoimmun 2003 21 201-12. 

Mor G, Yamshchikov G, Sedegah M. Induction of neonatal tolerance by plasmid DNA vaccination of mice./. Clin.Invest. 1996 98 2700-2705. 

Field AC, Caccavelli L, Bloch MF, Bellon B (2003) Regulatory CD8+ T cells control neonatal tolerance to a Th2-mediated autoimmunity. J Immunol, 170(5) 2508-2515. 

Powell TJ, Streilein JW. Neonatal tolerance induction by class II alloantigens activates IL-4 secreting, tolerogen-responsive T-cells. J Immunol 1990 144 854-859. 

Ridge, J. R, Fuchs, E. J. and Matzinger, R, Neonatal tolerance revisited turning on newborn T cells with dendritic cells. Science, 271, 1723, 1996. 

Yellen, A J., et al. Signaling through surface IgM in tolerance-susceptible immature murine B lymphocytes. Developmentally regulated differences in transmembrane signaling in splenic B cells from adult and neonatal mice, J Immunol., 146, 1446, 1991. 

Korotkova, M., Telemo, E., Flanson, L. A., and Strandvik, B. (2004). Modulation of neonatal immunological tolerance to ovalbumin by maternal essential fatty acid intake. Pediatr. Allergy Immunol. 15,112-122. 

Even if a medication is available in multiple formulations and dosage forms, the prescriber must consider the absorption and distribution differences between adult and pediatric patients. Blood supply at injection or infusion site, available blood supply for unit muscle mass, and skeletal muscle mass relative to body mass vary with patient age and size, causing drug absorption to vary, as well. A rapid intravenous bolus in a pediatric patient might result in acute toxicity a slow intravenous infusion, often required in neonates, can cause erratic, unreliable drug delivery in an older child. In addition, the volume of fluid tolerated for intravenous delivery varies significantly with the age and size of the patient. The blood supply and blood flow to and from the injection site are of prime importance since a gradual decrease in blood supply per unit muscle mass is seen with maturation. In addition, the skeletal muscle mass relative to... 

In 534 individuals aged 30 years, whose mothers had participated in a double-blind, randomized, placebo-controlled trial of antenatal betamethasone (two intramuscular doses 24 hours apart) for the prevention of neonatal respiratory distress syndrome, there were no differences between those exposed to betamethasone and placebo in body size, blood lipids, blood pressure, plasma cortisol, prevalence of diabetes, or history of cardiovascular disease (397). After the oral glucose tolerance test, those who had been exposed to betamethasone had higher plasma insulin concentrations at 30 minutes (61 versus 52 mIU/1) and lower glucose concentrations at 120 minutes (4.8 versus 5.1 mmol/1) than did those exposed to placebo. Antenatal exposure to betamethasone might result in insulin resistance in adult offspring, but has no effect on cardiovascular risk factors at 30 years of age. 

---