Virgin olive oil and its phenol fraction modulate monocyte/macrophage functionality: a potential therapeutic strategy in the treatment of systemic lupus erythematosus

5 FigurasMonocytes and macrophages are critical effectors and regulators of inflammation and innate immune response, which appear altered in different autoimmune diseases such as systemic lupus erythematosus (SLE). Recent studies suggested that virgin olive oil (VOO) and particularly its phenol compounds might possess preventive effects on different immune-inflammatory diseases, including SLE. Here, we evaluated the effects of VOO (and sunflower oil) on lipopolysaccharide (LPS)-activated peritoneal macrophages from a model of pristane-induced SLE in BALB/c mice, as well as those of the phenol fraction (PF) from VOO on the immune-inflammatory activity and plasticity in monocytes and monocyte-derived macrophages from healthy volunteers. The release of nitrite and inflammatory cytokines was lower in LPS-treated peritoneal macrophages from pristane-SLE mice fed the VOO diet when compared with the sunflower oil diet. PF from VOO similarly decreased the secretion of nitrite and inflammatory cytokines and expression of inducible nitric oxide, PPARγ and Toll-like receptor 4 in LPS-treated human monocytes. PF from VOO also prevented the deregulation of human monocyte subset distribution by LPS and blocked the genetic signature of M1 macrophages while favouring the phenotype of M2 macrophages upon canonical polarisation of naïve human macrophages. For the first time, our study provides several lines of in vivo and in vitro evidence that VOO and PF from VOO target and counteract inflammatory pathways in the monocyte–macrophage lineage of mice with pristane-induced SLE and of healthy subjects, which is a meaningful foundation for further development and application in preclinical and clinical use of PF from VOO in patients with SLE.M. A.-S. gratefully acknowledges support from a Postgraduate National Program of FPU fellowship and financial sponsorship from the Spanish Ministerio de Educación, Cultura y Deporte. S. M.-d. l. P. has the benefit of a FPI fellowship (BES-2012-056104) of MICINN. B. B. and S. M.-d. l. P. acknowledge support from ‘V Own Research Plan’ (University of Seville). The authors gratefully acknowledge the assistance of Centre for Technology and Innovation Research, University of Seville (CITIUS). The authors thank I+D+i of Oleoestepa SAC for kindly providing the VOO. This study was supported by research grants AGL2011-26949 and AGL2011-29008 (Spanish Ministry of Science and Innovation, MICINN) and P-10AGR-6609 (Junta de Andalucía). M. A.-S. and S. M.-d. l. P. performed cell cultures, cytokine measurements and RT-qPCR and western blot experiments. S. M.-d. l. P. and B. B. performed flow cytometry experiments and analysed the data. M. A.-S., S. M.-d. l. P. and F. J. G. M. wrote the main manuscript. C. A. d. l. L., M. S.-H. and F. J. G. M. designed and supervised the project and revised the paper. All authors discussed the results and implications and commented the manuscript at all stages. The authors declare that there are no conflicts of interest