Abstract
Glutamine is utilized at a high rate by some cells of the immune System (including
lymphocytes and macrophages) and is essential for the viability and normal functioning
of these cells. Experiments on lymphocytes in vitro showed that the proliferative response of these cells was dependent on the concentration
of glutamine and this suggests that a decrease in plasma glutamine concentration could
be responsible, at least in part, for the reported impairment of immune function in
various conditions. Much of the glutamine that enters the body is utilized by cells
of the small intestine, so that muscle is an important source for the plasma glutamine,
Hence, the plasma concentration of glutamine represents a “metabolic link” between
skeletal muscle and cells of the immune system. Indeed, the flux-generating step of
glutamino metabolism in cells of the immune system is considered to be located in
skeletal muscle which synthesizes and stores glutamine. The flux generating step is
probably the outward transport of glutamine across the plasma membrane. The rate of
this transport process and therefore glutamine release from muscle is decreased in
conditions associated with a reduction in immune function or activity in the rat such
as sustained exercise. The plasma glutamine concentration in man is decreased in a
number of pathological conditions, with the largest decrease recorded following major
burns. It is also decreased after prolonged exercise (e.g. marathon run) and in the overtrained state. It is suggested, therefore, that sustained
physical activity could damage the glutamine release process so that it does not respond
adequately to increased glutamine requirement by the immune system. The plasma glutamine
level therefore decreases resulting in an impairment of the function of the immune
system.
Alternatively since long chain fatty acids inhibit mitogen-stimulated lymphocyte proliferation
and since unsaturated fatty acids caused greater inhibition than saturated fatty acids,
this allows another explanation for immunosuppression in the overtrained state to
be proposed. These effects of polyunsaturated fatty acids are seen with cells obtained
from a variety of sources including rat lymph nodes, spleen, thymus or thoracic duct
and human peripheral blood or tonsils. T-cell proliferation was more sensitive to
the inhibitory effects of fatty acids than B-cell proliferation. In prolonged exercise,
changes in the composition of fatty acids available for immune cells could influence
their ability to respond to an immune challenge. Further work is needed to test this
hypothesis.
Key words
Glutamine - lymphocytes - muscle - unsaturated fatty acids - exercise
