Divergent effects of infliximab and anakinra therapies on macrophage phenotype from patients with refractory rheumatoid arthritis

International Journal of Immunopathology and Pharmacology
T N Q PhamVernon J Richardson

Abstract

Previously, we documented the co-expression of the inducible nitric oxide synthase (NOS2) and protein kinase C-eta (PKC-eta) in peripheral blood-derived macrophages (PBDM) from moderate to severe rheumatoid arthritis (RA) patients with elevated plasma nitric oxide levels but not from those with non-inflammatory osteoarthritis (OA) or normal plasma NO levels. The presence of PKC-eta was found to be required before macrophages could acquire the NOS2-positive phenotype and make copious levels of NO. In the current study, we report the divergent effects of two biological-based RA therapies which target TNFalpha function (infliximab) or IL1 response (anakinra) on the development of the NOS2-positive phenotype by PBDM in patients with refractory RA. Both infliximab and anakinra were effective in improving disease symptoms. However, treatment with anakinra, but not infliximab led to a complete suppression of NOS2 expression in PBDM and consequently, a more pronounced reduction in plasma NO levels. Data also revealed a requirement of both TNF-alpha and IL-1 in the development of the NOS2-positive macrophage phenotype. Finally, the data have shed light on the molecular mechanisms by which NO production may be regulated during disease pr...Continue Reading

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Citations

Jun 5, 2014·Immunotherapy·Mariana H García-HernándezDiana Patricia Portales-Pérez
Oct 11, 2013·Basic & Clinical Pharmacology & Toxicology·Tiina LeppänenEeva Moilanen
Apr 25, 2016·Current Rheumatology Reports·Davide FirinuStefano R Del Giacco
Jun 4, 2019·International Reviews of Immunology·Shachi Pranjal VyasRitobrata Goswami

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