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Animal studies have shown that the selective small-molecule inhibitor 3-(3-pyridinyl)-1-(4-pyridinyl)-2-propen-1-one (3PO), targeting the key glycolytic enzyme Phosphofructokinase-2/fructose-2,6-bisphosphatase 3 (PFKFB3), disrupts T cell metabolism, culminating in reduced cell proliferation and heightened cell death rates

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, providing oxaloacetate or boosting ETC flux) pushed macrophages towards an M2 profile (21)

Moreover, D-lactate interfered with M1 polarization provide survival advantage in acute inflammation (137)