The online version of this article (https://doi.org/10.1186/s12974-017-1042-z) contains supplementary material, which is available to authorized users.
Although the exact etiology of obsessive-compulsive disorder (OCD) is unknown, there is growing evidence of a role for immune dysregulation in the pathophysiology of the disease, especially in the innate immune system including the microglia. To test this hypothesis, we studied inflammatory markers in monocytes from pediatric patients with OCD and from healthy controls.
We determined the percentages of total monocytes, CD16+ monocytes, and classical (CD14highCD16−), intermediate (CD14highCD16low), and non-classical (CD14lowCD16high) monocyte subsets in 102 patients with early-onset OCD and in 47 healthy controls. Moreover, proinflammatory cytokine production (GM-CSF, IL-1β, IL-6, IL-8, and TNF-α) was measured by multiplex Luminex analysis in isolated monocyte cultures, in basal conditions, after exposure to lipopolysaccharide (LPS) to stimulate immune response or after exposure to LPS and the immunosuppressant dexamethasone.
OCD patients had significantly higher percentages of total monocytes and CD16+ monocytes than healthy controls, mainly due to an increase in the intermediate subset but also in the non-classical monocytes. Monocytes from OCD patients released higher amounts of GM-CSF, IL-1β, IL-6, IL-8, and TNF-α than healthy controls after exposure to LPS. However, there were no significant differences in basal cytokine production or the sensitivity of monocytes to dexamethasone treatment between both groups. Based on monocyte subset distribution and cytokine production after LPS stimulation, patients receiving psychoactive medications seem to have an intermediate inflammatory profile, that is, lower than non-medicated OCD individuals and higher than healthy controls.
These results strongly support the involvement of an enhanced proinflammatory innate immune response in the etiopathogenesis of early-onset OCD.
Additional file 1: Figure S1. Gating strategy for identification of monocyte subpopulations. (DOCX 324 kb)
Additional file 2: Table S1. Analysis of the percentages of total monocytes, monocyte subpopulations, and cytokine levels after LPS stimulation of purified monocytes in early-onset OCD diagnosed with different comorbidities. (DOCX 22 kb)
Additional file 3: Table S2. Correlations between the five proinflammatory cytokines measured in the study in basal conditions and after LPS or LPS-dexamethasone stimulation. (DOCX 21 kb)
Additional file 4: Table S3. Correlations between the monocyte subsets and the levels of the five proinflammatory cytokines measured in the study in basal conditions and after LPS or LPS-dexamethasone stimulation. (DOCX 23 kb)
Additional file 5: Table S4. Cytokine secretion by purified monocytes of early-onset OCD and healthy controls. (DOCX 24 kb)
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- Inflammatory dysregulation of monocytes in pediatric patients with obsessive-compulsive disorder
E. Azucena González-Navarro
- BioMed Central