Hydrogenated Soy Phosphatidylcholine Liposomes Stimulate Differential Expression of Chemokines And Cytokines by Rat Alveolar Macrophages In Vitro.

• HSPC liposomes with different surface properties (uncharged, PEGylated, cationic, anionic) induce differential patterns of cytokine and chemokine expression by rat alveolar Nr8383 macrophages in vitro in mono-culture in a concentration-dependent manner. • Uncharged liposomes exert the greatest effects on chemokine and cytokine expression by alveolar macrophages, inducing the expression of RANTES, GroKC, IL-2 and IL-4 at 0.1 mg/ml. Charged and PEGylated liposomes only exhibited an increase in IL-2 secretion at this concentration. • At 1 mg/ml, all liposomes significantly increased the secretion of IL-2, IL-4, VEGF and IL-18, but reduced the secretion of MIP1. • HSPC liposomes stimulated the secretion of both pro- and anti-inflammatory cytokines/chemokines, but may have also stimulated the differentiation of these M0 macrophages into a M2 phenotype. • The data suggest that depending on liposome surface properties, inhaled exposure to liposomes may affect the lungs susceptibility to infections and inhaled toxicants, its ability to resolve lung injury and adjuvant properties when delivered with inhaled vaccines. Liposomes are being developed as inhalable drug delivery systems, but concerns remain about their impact on the lungs. To better understand the impact of liposomes and their physicochemical properties on alveolar macrophages, the cytokine and chemokine expression profile of rat alveolar Nr8383 macrophages exposed to 0.1 and 1 mg/ml hydrogenated soy phosphatidylcholine (HSPC) liposomes was examined. Expression patterns varied considerably between liposomes in a concentration-dependent manner, with both anti- and pro-inflammatory chemokines/cytokines produced. Uncharged liposomes induce the greatest production of cytokines and chemokines, followed by PEGylated liposomes. The most significant increase in cytokine/chemokine expression was seen for IL-2 (up to 24-fold), IL-4 (up to 5-fold), IL-18 and VEGF (up to 10-fold), while liposome exposure significantly reduced MIP1 expression (5-fold). In summary, we demonstrate that liposome surface properties promote variable patterns of cytokine and chemokine secretion by alveolar macrophages. This suggests that the type of liposome employed may influence the type of immune response generated in the lung and by extension, dictate how inhaled liposomal nanomedicines affect the lungs response to inhaled toxicants and local infections. [ABSTRACT FROM AUTHOR]