title: Effects of bortezomib on the immune system: a focus on immune regulation.
abstract: Bortezomib, the first-in-class proteasome inhibitor, has become one of the standard treatments in multiple myeloma. The agent is thought to exert its antimyeloma effects through the inhibition of NF-κB. However, evidence suggests that bortezomib also affects additional cell survival pathways, such as the p44/42 mitogen-activated protein kinase pathway, and inhibitory effects on IL-6, TNF-α, and vascular endothelial growth factor have also been demonstrated. These diverse effects have prompted the investigation of bortezomib's activity in various immune and inflammatory processes. This review summarizes the data reported with bortezomib in the prevention of graft-versus-host disease, antibody-mediated graft rejection, and anti-angiogenesis and in the treatment of rheumatoid arthritis, multiple sclerosis, and other inflammatory diseases. The positive results obtained suggest a role for bortezomib in these different indications, and therefore further investigations are warranted.
authors.affiliation: Service d'Hématologie Clinique et de Thérapie Cellulaire, Hôpital Saint-Antoine, Paris, France; INSERM, UMRs 938, Paris, France; Universite Pierre & Marie Curie, Paris, France. Electronic address: mohamad.mohty@inserm.fr.
authors.forename: Mohamad
authors.initials: M
authors.lastname: Mohty
authors.forename: Eolia
authors.initials: E
authors.lastname: Brissot
authors.forename: Bipin N
authors.initials: BN
authors.lastname: Savani
authors.forename: Beatrice
authors.initials: B
authors.lastname: Gaugler
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology*; D001897:Boronic Acids / Q000494:pharmacology*; D000069286:Bortezomib; D006801:Humans; D007107:Immune System / Q000187:drug effects*; D009101:Multiple Myeloma / Q000188:drug therapy* / Q000276:immunology*; D011719:Pyrazines / Q000494:pharmacology*
chemical_list: D000970:Antineoplastic Agents; D001897:Boronic Acids; D011719:Pyrazines; D000069286:Bortezomib
keywords: Bortezomib; Graft-versus-host disease; Immune system; Proteaome inhibitor