A study by Rasouli et al., published in the Journal of Immunology reports that treatment-naive multiple sclerosis (MS) patients had greater numbers of GM-CSF+ T cells in the peripheral blood, whereas CD4+ and CD8+ T cells in MS brain lesions expressed GM-CSF. In addition, interferon (INF)-β suppressed GM-CSF production by T cells, in vitro conditions.
Granulocyte-macrophage colony-stimulating factor is a multipotent cytokine that prompts the proliferation of bone marrow-derived macrophages and granulocytes. Reports have identified monocytes as the primary target of GM-CSF.
This cytokine first drew attention when a clinical report in 1998, which assessed cytokine concentrations in the cerebral spinal fluid of MS patients with active disease, found that the levels of the cytokine are significantly increased in MS patients compared to healthy controls.
McQualter and colleagueswanted to determine whether this cytokine played a critical and non-redundant role in promoting EAE pathology. This study is the first to underscore the critical role of GM-CSF in potentiating EAE pathology. Based on their findings and the aforementioned clinical study, McQualter and colleagues posited that this cytokine is a putative therapeutic target for MS treatment.
In the Journal of Immunology study, Rasouli et al. from the Department of Neurology, Thomas Jefferson University, Philadelphia, found significantly greater numbers of GM-CSF-producing CD4+and CD8+T cells in peripheral blood (PB) of untreated MS patients compared with patients undergoing IFN-beta therapy and healthy controls. In agreement with this ex vivo analysis, IFN-beta suppressed this cytokine production by T cells in vitro.
According to the authors their observations suggest that the greater frequency of the cytokine–producing T cells may contribute to MS immune pathogenesis, or on the other hand, this may represent only an epiphenomenon of abnormally activated immune cells in MS.
Recent multiple sclerosis (MS) research in animal models showed an important role of granulocyte macrophage colony-stimulating factor. This new study using human samples, by Javad Rasouli and co-workers further reinforces the role of this cytokine .
Granulocyte-macrophage colony-stimulating factor is increasingly recognized as a pivotal cytokine in the pathogenesis of MS.Its production by multiple immune cell types is increased in MS, and its levels in the CSF correlate with disease activity. Moreover, the cytokine is implicated in the pathological mechanisms of EAE. The blockade of this cytokine signalling prevents or suppresses EAE.
These studies strongly support interventions to block GM-CSF in MS, and results from phase I studies indicate a favourable safety profile of antibodies against this cytokine .