Granulocyte-macrophage colony-stimulating factor negatively regulates early IL-10-mediated responses

Abstract

Aim:

Treatment of inflammatory disorders relies on the intervention in immune responses thereby restoring homeostasis. IL-10 is a cytokine with therapeutic potential, but until now has not been as successful as previously anticipated. A reason for this may be that IL-10 responsiveness depends on the environment of the inflamed tissue. In this study we investigated whether GM-CSF is able to influence IL-10-mediated responses.

Methodology:

Dendritic cells and macrophages were differentiated from mouse bone marrow and treated or depleted from GM-CSF prior to analyze their response to IL-10. Activity was assessed by measuring cytokine expression upon lipopolysaccharide stimulation, IL-10-induced signaling and down-stream gene expression.

Conclusion:

This study describes that GM-CSF negatively regulates IL-10-mediated responses.

Lay abstract

Over the last couple of decades inflammatory disorders, like autoimmune disease and allergies, are becoming more prevalent in the western world. These inflammatory disorders are characterized by uncontrolled immune responses against harmless antigens or commensal bacteria. Treatment of these diseases relies on the intervention in inflammatory responses and thereby restoring the balance of the immune system. One approach used in the clinic to balance the immune system is by treating patients with molecules used by our own immune system to suppress inflammation, such as IL-10. However, treatment with IL-10 has not been as successful as previously anticipated. In this study we show that a particular signaling molecule of the immune system that contributes to inflammation negatively affects the response of immune cells toward IL-10 and thereby could contribute to the low efficacy of IL-10 treatment.