title: Modulation of mouse macrophage polarization in vitro using IL-4 delivery by osmotic pumps.
abstract: 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.
authors.affiliation: Orthopaedic Research Laboratories, Department of Orthopaedic Surgery, Stanford University School of Medicine, Stanford, California.
authors.forename: Jukka
authors.initials: J
authors.lastname: Pajarinen
authors.forename: Yasunobu
authors.initials: Y
authors.lastname: Tamaki
authors.forename: Joseph K
authors.initials: JK
authors.lastname: Antonios
authors.forename: Tzu-Hua
authors.initials: TH
authors.lastname: Lin
authors.forename: Taishi
authors.initials: T
authors.lastname: Sato
authors.forename: Zhenyu
authors.initials: Z
authors.lastname: Yao
authors.forename: Michiaki
authors.initials: M
authors.lastname: Takagi
authors.forename: Yrjö T
authors.initials: YT
authors.lastname: Konttinen
authors.forename: Stuart B
authors.initials: SB
authors.lastname: Goodman
mesh_terms: D000818:Animals; D001854:Bone Marrow Cells / Q000166:cytology; D016764:Cell Polarity / Q000187:drug effects*; D017077:Culture Media, Conditioned / Q000494:pharmacology; D015847:Interleukin-4 / Q000494:pharmacology*; D008070:Lipopolysaccharides / Q000494:pharmacology; D008264:Macrophages / Q000166:cytology* / Q000187:drug effects; D008297:Male; D008810:Mice, Inbred C57BL; D009995:Osmosis; D010641:Phenotype
chemical_list: D017077:Culture Media, Conditioned; D008070:Lipopolysaccharides; D015847:Interleukin-4
keywords: inflammation; interleukin-4; macrophage polarization; osmotic pumps; osteolysis; total joint replacement