Influence of glutamine on cytokine production in vitro

Increased availability of glutamine enhanced interleukin (IL)-2 production by concanavalin A (Con A)-stimulated rat (Calder and Newsholme, 1992), mouse (Yaqoob and Calder, 1997) and human (Rohde et al., 1996a; Yaqoob and Calder, 1998; Chang et al., 1999b) lymphocytes and also increased expression of the IL-2 receptor on stimulated rat lymphocytes (Yaqoob and Calder, 1997). The latter study also reported that the proportion of CD4+ lymphocytes increased with increasing concentration of glutamine in the culture medium (Yaqoob and Calder, 1997). Interferon (IFN)-7 production by human blood lymphocytes was enhanced with increasing availability of gluta-mine (Heberer et al., 1996; Rohde et al., 1996a; Yaqoob and Calder, 1998; Chang et al., 1999b), with maximum production occurring at a concentration below 0.5 mM.

Wallace and Keast (1992) demonstrated that murine macrophages stimulated with bacterial LPS secreted increasing amounts of IL-1 as the supply of glutamine increased, while more recently Murphy and Newsholme (1999) reported similar enhancement of tumour necrosis factor (TNF)-a release by rat macrophages with increasing glutamine availability. Glutamine addition to cultured rat macrophages stimulated with LPS increased IL-1p and IL-6 mRNA and secreted protein levels (Yassad et al., 2000). In contrast to the observations with rodent macrophages, production of TNF-a, IL-1 p and IL-6 by human blood monocytes (Rohde et al., 1996a; Yaqoob and Calder, 1998) and lymphocytes (Heberer et al., 1996) appears to be little affected by glutamine availability, although one study suggests otherwise for IL-6 production (Peltonen et al., 1997). IL-8 production by LPS-stimulated human blood monocytes was markedly increased with increasing glutamine concentration (Murphy and Newsholme, 1999).

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