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Glutamine as the Key Amino Acid in Promoting Cell-Mediated Immunity: 20 Years of Clinical Experience
|Author article list|
Renato Cocchi M.D., Ph.D. (Sociology)
Paper presented at the 6th International Congress on Amino Acids, Bonn 1999
Reprinted with the permission of Renato Cocchi|
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Normal and Down children with easiness to upper respiratory tract infections (URTI) had favourable treatment by Gabaergic drugs. Research showed that stress undermines host resistance to infections through neuroendocrine mediated changes in immuno-competence. It is the same for every kind of stress, even for internal metabolic stress due to a chromosomal anomaly, as it happens in Down syndrome.
Because the immune suppressive action of stress via the GABA impairment and subsequent cortisol hyperincretion or hyperactivity, it has been explained the rationale to counteract this easiness by drugs, one of which is glutamine. This drug is also directly involved in the nucleogenesis of rapid proliferating cells, by this way contributing to a larger production of leukocytes. Key words: Glutamine, URTI easiness, Stress, GABAergic drugs, Nucleogenesis, Leukocytes.
Since the pioneering study in depressed children (Cocchi, 1981) normal and Down children with easiness to upper respiratory tract infections (URTI) had favourable treatment by Gabaergic drugs (Cocchi, 1998a; 1998b). This immune-protective effect in Down children appears early before the age-related decreasing of easiness to upper respiratory tract infections (Cocchi 1997, 1998a).
Profound forms of URTI easiness stop at the 8-10 years' interval in drug-treated Ss, but at the 14-16 years' interval in non treated Ss. Severe forms in non treated Ss are again 10% while they are only 5% in drug-treated Ss, at more than 16 years.
Metabolic stress, in Down Ss, could relate to the "dosage effect" of the third chromosome 21 (Cocchi 1994). Research showed that stress undermines host resistance to infections through neurendocrine mediated changes in immune competence (Boyce et al., 1995). It is the same for every kind of stress of external or internal origin or both. The adrenergic blockade improves also cellular immune responses otherwise depressed by the so called mental stress in humans as one type of internal stresses (Bachen et al.,1995).
Because the immune-suppressive action of stress via the GABA impairment (Horger and Roth, 1995) and subsequent cortisol hyper-incretion or hyper-activity (Dhabhar et al., 1996; Haessig et al., 1996; Dantzer, 1997; Friedman and Irwin, 1997), the rationale of the treatment to counteract this easiness by drugs has its explanation as it follows.
The basic treatment uses Gabaergic drugs like l-glutamine as the precursor of GABA via l-glutamic acid (Laake et al., 1995; Shupliakov et al., 1997). Pyridoxine is the cofactor of all decarboxylases, GAD inclusive (Baxter, 1976).
Finally, a benzodiazepine is the sensitizer of type A Gabaergic receptors and a powerful antistress agent (Bruni et al., 1980; Viukari, 1983; Schoch et al., 1985).
In 1-14 years children we can prescribe the following:
This 3-drugs' prescription works in a synergistic way and can restore the glutamic-GABA pathway impaired by the stress itself. The use of a benzodiazepine aims to resensitize type A Gabaergic receptors, the first metabolic point where stress applies itself. Without doing it we could induce only the increasing of the glutamate with hazardous effects.
This evening use of a benzodiazepine is the best way to restore sleep ( Viukari, 1983) often impaired by excess adrenergic stimulation. Moreover, it can to avoid side-effects like daily drowsiness and muscle relaxation.
On the other hand l-glutamine is directly involved in the nucleogenesis of rapid proliferating cells (Gismondo et al., 1998). Namely it is the donor of the N atoms 3 and 9 of the purinic ring (Stryer, 1988). By this way it contributes to a better production of leukocytes (Heberer et al., 1996; Newsholme & Calder 1997; Yoo, et al., 1997).
A personal anecdotal experience (non yet published) strongly suggests also the use of this antistress therapy in HIV+ Ss. It can lead to increase the leucocytes production both by reducing the metabolic stress due to the illness itself and by favouring the nucleogenesis.
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