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Updated: May 2, 2026
Reprograming Model of Human Monocyte-derived Macrophages for In-vitro Assays
Published on: April 18, 2025
Macrophages and depression - a misalliance or well-arranged marriage?
Adam Roman1, Grzegorz Kreiner, Irena Nalepa
1Department of Brain Biochemistry, Institute of Pharmacology, Polish Academy of Sciences, Smętna 12, PL 31-343 Kraków, Poland. roman@if-pan.krakow.pl.
Abstract:
Depression is a severe medical condition with multiple manifestations and diverse, largely unknown etiologies. The immune system, particularly macrophages, plays an important role in the pathology of the illness. Macrophages represent a heterogeneous population of immune cells that is dispersed throughout the body. The central nervous system is populated by several types of macrophages, including microglia, perivascular cells, meningeal and choroid plexus macrophages and pericytes. These cells occupy different brain compartments and have various functions. Under basal conditions, brain macrophages support the proper function of neural cells, organize and preserve the neuronal network and maintain homeostasis. As cells of the innate immune system, they recognize and react to any disturbances in homeostasis, eliminating pathogens or damaged cells, terminating inflammation and proceeding to initiate tissue reconstruction. Disturbances in these processes result in diverse pathologies. In particular, tissue stress or malfunction, both in the brain and in the periphery, produce sustained inflammatory states, which may cause depression. Excessive release of proinflammatory mediators is responsible for alterations of neurotransmitter systems and the occurrence of depressive symptoms. Almost all antidepressive drugs target monoamine or serotonin neurotransmission and also have anti-inflammatory or immunosuppressive properties. In addition, non-pharmacological treatments, such as electroconvulsive shock, can also exert anti-inflammatory effects. Recent studies have shown that antidepressive therapies can affect the functional properties of peripheral and brain macrophages and skew them toward the anti-inflammatory M2 phenotype. Because macrophages can affect outcome of inflammatory diseases, alleviate sickness behavior and improve cognitive function, it is possible that the effects of antidepressive treatments may be, at least in part, mediated by changes in macrophage activity.
Insights
Depression may be linked to chronic inflammation involving macrophages. Antidepressant therapies might work by shifting these immune cells, particularly brain macrophages, towards an anti-inflammatory state.
Area of Science:
- Neuroscience
- Immunology
- Psychiatry
Background:
- Depression is a complex medical condition with poorly understood causes.
- The immune system, especially macrophages, plays a significant role in depression's pathology.
- Macrophages in the central nervous system (microglia, perivascular cells, etc.) maintain brain homeostasis and respond to disturbances.
Purpose of the Study:
- To explore the role of macrophages in the development of depression.
- To investigate how antidepressant treatments impact macrophage function.
Main Methods:
- Review of existing literature on depression, immune system involvement, and macrophage biology.
- Analysis of studies examining the effects of antidepressant therapies on macrophage phenotypes.
Main Results:
- Sustained inflammatory states, driven by excessive proinflammatory mediators, can contribute to depressive symptoms.
- Antidepressant drugs and non-pharmacological treatments often possess anti-inflammatory properties.
- Emerging evidence suggests antidepressant therapies can modulate macrophage activity, promoting an anti-inflammatory M2 phenotype.
Conclusions:
- Macrophage activity and phenotype may be a key factor in depression.
- The anti-inflammatory effects of antidepressants on macrophages could be a primary mechanism of action.
- Targeting macrophage function represents a potential therapeutic strategy for depression.
