Macrophages are phagocytic cells involved in a number of functions that secrete a large number of cytokines, chemokines and growth factors that can activate different cell types and play a role in inflammation. Macrophages can be classically or alternatively activated, obtaining either the pro-inflammatory phenotype M1 or the anti-inflammatory phenotype M2. Inflammatory cytokines, such as TNF-a and IFN-gamma are known to provoke a M1 phenotype but the mechanism responsible are unknown. Ivns1abp is a gene coding for a 642 amino acid protein that localizes to both the nucleus and the cytoplasm. Functioning as a homodimer, Ivns1abp associates with F-actin and, via this association, plays an important role in the organization and stabilization of the actin skeleton. The aim of this work was to study the mechanism involved in cytokine regulation of macrophage phenotype switch. For this purpose, murine BMDMs, obtained by Swiss CD1 mice, sacrificed by an overdose of isoflurane, were cultured in presence of GM-CSF during 7 days to achieve macrophage phenotype. After this period of time macrophage overexpressing ivns1abp and control macrophages in the presence or absence of cytokines and c-myc inhibitors were cultured to evaluate cytokines, ivns1abp and c-myc production. Results indicated that cytokines provoke a a decrease in Ivns1abp, c-myc expression, M2 cytoskeletal features and anti-inflammatory mediators ( IL-10, mannose receptor), showing an increase in M1 cytoskeletal features . C-myc inhibitors provoked the same results indicating that cytokines act on c-myc to down regulate ivns1abp, anti-inflammatory mediators and cytoskeletal M2 features. Based on these results, we conclude that cytokines trough its inhibitory action on c myc, down regulates ivns1abp expression that in turns provokes a phenotype change trough cytoskeleton stabilization.