A myriad of inflammatory cytokines are released when macrophages are activated, which produces a microenvironment responsible for the proinflammatory state and leukocyte recruitment. The treatment of macrophages with P2C7 not only modulated the expression of genes related to M1 polarization but also increased the translation of proteins important for the proinflammatory response as TNF-α and CCL2. TNF-α is closely related to the modulation of the M1 phenotype and CCL2 is important in the recruitment of monocytes, memory T cells, and dendritic cells to sites of tissue injury. The expression of this proinflammatory chemokines is increased in atherosclerotic lesions [41], and CCL2-induced expression by oxLDL is associated with TNF-α [42]. Although TGF-β mRNA—a M2 polarization marker—was not upregulated by P2C7, the expression of IL-10 mRNA —an anti-inflammatory interleukin associated with the M2 phenotype—was induced by the P2C7 peptide and LDL (−). These observations agree with previous data showing the release of IL-10 from leukocytes treated with LDL (−) [33]. M2 macrophages can polarize into M2a (inflammation resolution/anti-inflammatory) and M2b/c (regulatory inflammation/anti-inflammatory [33]. In particular, M2b macrophage polarization occurs via proinflammatory stimuli, such as LPS or DAMPs plus IL-1β, and these cells express high levels of IL-10 along with inflammatory cytokines [43]. In this context, we can suggest that only a small population of BMDM was polarized to M2b by P2C7 increasing IL-10 mRNA without the corresponding increase of the cytokine in the supernatant of macrophage cultures, which probably occurred because its level was below the detection limit of the analytical method used in this study.