Modulation of mouse macrophage polarization in vitro using IL-4 delivery by osmotic pumps

Modulation of macrophage polarization is emerging as promising means to mitigate wear particle‐induced inflammation and periprosthetic osteolysis. As a model for continuous local drug delivery, we used miniature osmotic pumps to deliver IL‐4 in order to modulate macrophage polarization in vitro from nonactivated M0 and inflammatory M1 phenotypes towards a tissue regenerative M2 phenotype. Pumps delivered IL‐4 into vials containing mouse bone marrow macrophage (mBMM) media. This conditioned media (CM) was collected at seven day intervals up to four weeks (week 1 to week 4 samples). IL‐4 concentration in the CM was determined by ELISA and its biological activity was assayed by exposing M0 and M1 mBMMs to week 1 or week 4 CM. The IL‐4 concentration in the CM approximated the mathematically calculated amount, and its biological activity was well retained, as both M0 and M1 macrophages exposed to either the week 1 or week 4 CM assumed M2‐like phenotype as determined by qRT‐PCR, ELISA, and immunocytochemistry. The results show that IL‐4 can be delivered using osmotic pumps and that IL‐4 delivered can modulate macrophage phenotype. Results build a foundation for in vivo studies using our previously validated animal models and provide possible strategies to locally mitigate wear particle‐induced macrophage activation and periprosthetic osteolysis. © 2014 Wiley Periodicals, Inc. J Biomed Mater Res Part A: 103A: 1339–1345, 2015.