Stimulatory effect of glutamine on human monocyte activation as measured by interleukin-6 and soluble interleukin-6 receptor release

The activation state of murine peritoneal macrophages is shown to depend on extracellular glutamine concentration. However, there are no studies on the effect of glutamine concentration on the activation state of human monocytes. We studied the effect of extracellular glutamine concentration on interleukin (IL-6) and soluble IL-6 receptor (sIL-6R) production by activated monocytes. Monocytes separated by density gradient centrifugation and adherence to glass from buffy coats obtained from healthy donors were activated by 1 pg/ml or 1 ng/ml lipopolysaccharide (LPS) and incubated for 48 h in 0, 0.1, 0.2, 0.6 and 2.0 mM glutamine. Levels of IL-6 and sIL-6R in culture medium were measured by immunoassay. The extracellular glutamine concentration had a significant effect on IL-6 secretion by activated human monocytes. The mean levels of IL-6 in 0.1 mM glutamine were only marginally higher (P= 0.54) compared to those in the absence of glutamine. A minimum of 0.2 mM glutamine was required to reach the maximal production of IL-6. At all glutamine concentrations the higher concentration of LPS (1 ng/ml) induced higher mean levels of IL-6 than the lower one (1 pg/ml). Glutamine concentration did not affect sIL-6R production. Our results indicate that very low levels of glutamine in plasma may impair the activation of human monocytes as measured by IL-6 secretion.