GLUTAMINE AS THE KEY AMINO ACID
IN PROMOTING CELL-MEDIATED IMMUNITY:
20 YEARS OF CLINICAL EXPERIENCE.
By Renato
COCCHI, MD, neurologist and medical psychologist
Abstract
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.
Drug modulation of stress reactions
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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:
- glutamine: 125-500 mg daily (not later
than 2 PM);
- pyridoxine 75-150 mg daily;
- diazepam 1-3mg in the evening (in small
children better oxazepam 5-8 mg, always in the evening).
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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Presented at the 6th International Congress on Amino acids, Bonn 1999.
Posted on internet on September 2001. Copyright by Renato Cocchi, 2001.
Author’s address : Renato COCCHII MD, via Rabbeno, 3
42100 Reggio Emilia
(Italy)
renatococchi@libero.it
Drug modulation of stress reactions
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