Dietary Modulation of Thymic Enzymes

Abstract

Malnutrition is a complex syndrome caused by an inadequate intake of energy, protein, minerals and vitamins which affects the immune system. Nutritional imbalances, present in children with energy-protein malnutrition and infections, make defining the specific effects of each of them on the thymus difficult. For this reason, it is necessary to design an experimental model in animals that could define a single variable. As the thymus atrophy described in humans is similar to that observed in murines, a rat experimental model makes the extrapolation to man possible. Some authors suggest that the activity of Adenosine Deaminase (ADA) and Purine Nucleoside Phosphorylase (PNP)--involved in purine metabolism--have an influence on T lymphocyte development and the immune system, due to intracellular accumulation of toxic levels of deoxynucleotides. Studies in our group, performed in an experimental model on Wistar growing rats, have demonstrated that protein deficiency or imbalance in the profile of essential amino acids in the diet, produce loss of thymus weight, reduction in the number of thymocytes, a diminished proportion of T cells presenting the W3/13 antigenic determinant and DNA content with concomitant increase in cell size, and the proportion of immature T cells and activity of ADA and PNP, without modifying the activity of 5´Nucleotidase in the thymus. It is important to point out that there were neither differences in energy intake between experimental groups and their controls, nor clinical symptoms of deficiency of other nutrients. The increase in these thymic enzyme activities was an alternative mechanism to avoid the accumulation of high levels of deoxynucleotides, which would be toxic for T lymphocytes. On the other hand, the administration of a recovery diet, with a high amount of high quality protein, was able to reverse the mentioned effects. The quick reply of Adenosine Deaminase to nutritional disorders and the following nutritional recovery, points out to this determination as a potential functional marker of nutritional status. Some authors have demonstrated an increase in ADA activity, in serum and other biological fluids in patients with various diseases involving defense mechanisms. According to these findings, it could be inferred that ADA activity in serum would follow the same behavior as observed in a rat thymus. So, we have analyzed if its determination could be considered a functional biochemical parameter in populations at nutritional risk. We analyzed the serum ADA activity in groups of individuals with altered nutritional status evaluated through different markers--young adult patients with Nervous Anorexia, overweight or obese school children, children suffering cystic fibrosis. The results show a statistically significant increase in the ADA activity in all groups, with respect to their healthy controls--same age range and socio economic status. The results obtained to date suggest the importance of including the determination of serum Adenosine Deaminase activity in the biochemical evaluation of the nutritional status, as a functional marker related to defense mechanisms.