Macrophages (MΦs) produce cytokines and control inflammatory responses. The production of cytokines by MΦs is regulated by various factors, including amino acids. The aim of this study was to elucidate the role of serine, a non-essential amino acid, in the production of cytokines. We first showed that cellular content of serine in MΦs was significantly decreased when cultured without serine, and this result indicates that MΦs are dependent on the serine present in extracellular spaces. 
We next showed that MΦs exhibited decreased production of interleukin (IL) 10, an anti-inflammatory cytokine, and increased production of IL6, a proinflammatory cytokine, in the absence of serine. Metabolome analysis showed that depletion of serine affected cellular metabolism of MΦs. We also found that cellular content of pyruvate, a crucial metabolite in the glycolytic pathway, was decreased. Administration of pyruvate to MΦs cultured without serine normalized the expression levels of IL10 and IL6. In conclusion, serine is crucial for the synthesis of pyruvate and contributes to adequate production of cytokines in MΦs. Thus, serine might be a novel target for anti-inflammatory drugs.