Anti-colony-stimulating factor therapies for inflammatory and autoimmune diseases

Abstract

Granulocyte-macrophage colony-stimulating factor (GM-CSF), macrophage colony-stimulating factor (M-CSF; also known as CSF1), granulocyte colony-stimulating factor (G-CSF) and interleukin-3 (IL-3) can each play a part in the host response to injury and infection, and there is burgeoning interest in targeting these CSFs in inflammatory and autoimmune disorders, as well as in cancer. For success in clinical medicine, therapeutic targeting will need to be delineated from current strategies. The individual CSFs have unique biological roles, suggesting that they could be used to target specific conditions. This Review compares the CSFs, with a focus on how they could be targeted, discusses the relevant clinical trial data and summarizes the potential clinical applications of targeting each CSF. Importantly, we discuss the novelty of CSF biology and attempt to clarify some of the surrounding misconceptions and issues that can affect therapeutic decisions.

Microglia mediate postoperative hippocampal inflammation and cognitive decline in mice

“…Importantly, CSF1R inhibitors are already in clinical trials for chronic diseases ranging from cancer to inflammatory arthritis (43)(44)(45). Perioperative CSF1R inhibition would be focused and short-lived by comparison, thus minimizing patient risk.…”

Avoidance of total knee arthroplasty in early osteoarthritis of the knee with intra-articular implantation of autologous activated peripheral blood stem cells versus hyaluronic acid: A randomized controlled trial with differential effects of growth factor addition

“…In concordance to the above results, early and sustained relief in pain was a significant finding in the present study followed by improvements in function as the latter may be compromised by excess pain. The effects of G-CSF on arthritic pain may be conflicting [57], but in some situations, G-CSF has even been considered to be an anti-inflammatory immunomodulator where the effects of systemic and/or local pharmacological exogenous doses of hG-CSF might differ from those of endogenous G-CSF [58]. Exogenous hG-CSF mobilizes hematopoietic cells from the bone marrow which, in turn, probably changes the composition of peripheral blood cell populations to less mature and perhaps less inflammatory phenotypes, thereby changing the nature of the dynamic cell populations available to migrate into the site of inflammation [58].…”

“…The effects of G-CSF on arthritic pain may be conflicting [57], but in some situations, G-CSF has even been considered to be an anti-inflammatory immunomodulator where the effects of systemic and/or local pharmacological exogenous doses of hG-CSF might differ from those of endogenous G-CSF [58]. Exogenous hG-CSF mobilizes hematopoietic cells from the bone marrow which, in turn, probably changes the composition of peripheral blood cell populations to less mature and perhaps less inflammatory phenotypes, thereby changing the nature of the dynamic cell populations available to migrate into the site of inflammation [58]. Moreover, hG-CSF appears crucial for skeletal myocyte development and regeneration [59] and positively affects the satellite cell population aiding the preservation of the satellite stem cell pool [60] which in turn supports long-term muscle regeneration and functional maintenance [60], all factors that may be behind improvements in function and stiffness observed in the present study.…”

Pathogenetic insights from the treatment of rheumatoid arthritis

“…IL-6 also p[lays a pivotal roel in comorbidity discussed below. Granulocyte-macrophage colony-stimulating factor (GM-CSF) is a pro-inflammatory soluble cytokine implicated by several previous studies in the pathogenesis of RA [24]. Via binding to GM-CSF receptor alpha (GM-CSFRα), GM-CSF activates neutropihls and macrophages in models of arthritis and macrophages and neutrophils in rheumatoid inflammatory tiossues ex vivo; recent clinical trials have been successful providing human proof of concept for a pivotal role [25].…”