Hence, the authors hypothesized that there may be a relationship between prolonged psychological stress and MDSCs. A mouse model using restraint as a chronic stressor was utilized, and bone marrow, spleen, and thymus were examined. The bone marrow and peripheral blood of stressed mice showed accumulation of CD11b+Gr1+ cells. PGE2 levels but not VEGF levels were found to be elevated, and catecholamines also appeared to play a role in MDSC accumulation, as β-adrenergic receptor blockade with propranolol partially reversed the noted accumulation.
As the biosynthetic pathway for PGE2 depends on the inducible cyclooxygenase 2 (COX-2) enzyme and catecholamines contribute to COX-2 induction under a pro-inflammatory environment, the authors suggest that the COX-2-PGE2 loop mediates the MDSCs accumulation downstream of catecholamines.
Of note, bone marrow CD11b+Gr1+ cells isolated from stressed mice produced more TNF-α upon LPS stimulation, but exhibited higher ability to induce the production of IL-10 in primary macrophages.
This study highlights the complex interplay between psychological stress and immunity and may reveal a new mechanism by which stress can induce immunosuppression.