Effects of decreased plasma glutamine concentrations on peripheral lymphocyte proliferation in rats

Abstract

The relationship between exercise-induced lowering of plasma glutamine concentrations and proliferation of peripheral lymphocytes was investigated in male Wistar rats. The T-lymphocyte proliferative responses to the mitogen, concanavalin A, were determined by incorporation of radiolabelled thymidine into the DNA in vitro. The rats ran 2 h x day(-1), 6 days x week(-1) for 4 weeks. Analysis immediately after the final period of exercise showed T-lymphocyte proliferation to be significantly depressed, together with a marked decrease in plasma glutamine concentrations. There were also significant increases in serum corticosterone concentrations immediately after exercise. However, following 24-h recovery, this exercise-induced immunosuppression was not statistically significant when compared with the age-matched control group. In the second experiment, in order to clarify the importance of glutamine for immunological function in vivo, methionine sulfoximine, an effective inhibitor of glutamine synthetase was injected intraperitoneally (12.5 mg x kg body mass[-1]). Plasma glutamine concentrations were decreased 4 h after the injection, compared with the placebo control group, and this resulted in a significant decrease in the rate of T-lymphocyte proliferation. This treatment had no effects on serum corticosterone concentrations. These results would suggest that the chronic exercise-induced reduction in proliferation of peripheral T-lymphocytes is a transient reversible phenomenon, which returns to normal levels within 24 h of the final training period. It is also conceivable that this exercise-induced immunosuppression is associated with a decrease in circulating glutamine concentrations.

Efeito da L-Glutamina sobre o perfil leucocitário e a função fagocítica de macrófagos de ratos estressados

“…A modulação do sistema imunológico, induzida pelo estresse já é um fenômeno bem conhecido 8,9 , estando descrita a ocorrência de neutrofilia, linfopenia e monocitose a seguir à exposição ao estímulo indutor da situação de estresse 6 . As funções anti-microbiana e antitumoral de macrófagos/monócitos parecem, também, diminuir 10 .…”

“…No hipercatabolismo a glutamina é reconhecida como aminoácido "condicionalmente essencial", e tem despertado interesse dos pesquisadores por sua capacidade de interferir no funcionamento de células do sistema imune 8,9,11 . Por exemplo, os macrófagos utilizam glutamina para realização da função fagocítica e citotóxica 12 .…”

Metabolic fate of glutamine in lymphocytes, macrophages and neutrophils

“…Mitogenic stimulation of lymphocytes increases both glutaminase activity and the rate of glutamine utilization (11). In the absence of glutamine, lymphocytes do not proliferate in vitro; proliferation increases greatly with glutamine concentration (12).…”

“…Glutamine utilization has also been shown to be associated with the production of superoxide and interleukin-1 and -6 (14) by macrophages and interleukin-2 by lymphocytes (15). Macrophage-mediated phagocytosis is influenced by glutamine availability (11). Beneficial effects of the provision of glutamine (16) or its precursors (17) have been reported in patients submitted to surgery, radiation treatment or bone marrow transplantation or suffering from injury, sepsis or burns (18).…”

As Fases Do Treinamento De Natação Influenciam Os Substratos Energéticos, Cortisol E Leucócitos

“…Por sua vez, a glutamina é um importante substrato para as células do sistema imune (CALDER, 1995;PEDERSEN et al, 1997;KOYAMA et al, 1998;AGOSTINI & BIOLO, 2010). O aumento do número de leucócitos é característico do estresse induzido pelo exercício, como consequência da proliferação de neutrófilos (PEDERSEN et al, 1997;RISOY et al, 2003).…”