Inflammatory dysregulation of monocytes in pediatric patients with obsessive-compulsive disorder

Abstract

BackgroundAlthough 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.MethodsWe 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.ResultsOCD 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.ConclusionsThese results strongly support the involvement of an enhanced proinflammatory innate immune response in the etiopathogenesis of early-onset OCD.Electronic supplementary materialThe online version of this article (10.1186/s12974-017-1042-z) contains supplementary material, which is available to authorized users.

What does immunology have to do with brain development and neuropsychiatric disorders?

“…In addition to these genetic and epidemiological findings, there is an emerging body of preliminary data that is focused on inflammatory markers (cytokine and immunoglobulin levels), immune cell populations, and gene expression profiling of peripheral lymphocytes. These data indicate some degree of hyperactivity of both the innate and the adaptive immune systems in TS, childhood-onset OCD and ADHD [131][132][133][134][135] .…”

Could neutrophil-to-lymphocyte ratio be an important parameter in children and adolescents with obsessive compulsive disorder? (eng)

“…In contrast to these findings, there are also studies showing a significant decrease in TNF-alpha (p <0.0001) in OCD patients compared to healthy controls (10). Although a 2018 meta-analysis in which 6 cytokines (TNF-α, IL-1β, IL-6, IL-4, IL-10 and IFN-1) were evaluated among patients with OCD found that the results of the studies were contradictory and that there was no consistent evidence for the involvement of immune mediators in the pathophysiology of OCD; this suggests the lability of cytokines (11). It has also been suggested that neutrophil and lymphocyte levels, which are more stable in chronic inflammation than blood cytokine levels, NLR may be a reliable proinflammatory marker.It has been found that proinflammatory susceptibility may be present in early-onset OCD patients due to the excessive reactivity of monocytes which are natural immune response cells (12).…”

ESTIMATION OF LEVEL OF SUBPOPULATION CD14⁺/CD16⁺ MONOCYTES IN PATIENTS WITH JUVENILE DEPRESSIONS

“…У больных юношескими депрессиями с синдромом аттенуированных психотических симптомов впервые выявлено значительное повышение количества провоспалительных моноцитов с фенотипом СD14 + /СD16 + по сравнению с их уровнем у здоровых. С нашей точки зрения, представленные результаты могут свидетельствовать о наличии скрытого иммунного воспаления у больных юношескими депрессиями, что согласуется с результатами, полученными в многочисленных исследованиях других системных заболеваний, в которых сообщается о значительном повышении у больных уровня провоспалительных моноцитов с фенотипом СD14 + /СD16 + [13,22,24,29,26]. Следует отметить, что при моделировании скрытого иммунного воспаления в экспериментальных исследованиях, направленных на изучение механизмов изменения уровня…”

“…Так, некоторые исследователи показали, что «классические» моноциты с фенотипом CD14 ++ /CD16выполняют функцию фагоцитов, но не принимают участие в воспалительных процессах [21]. Mоноциты с фенотипом CD14 + /CD16 + являются антигенпрезентирующими клетками и осуществляют воспалительные реакции, продуцируя провоспалительные цитокины TNFα [13,24] и IL-1β [22]. При этом в ряде работ было показано, что избыток TNFα в крови является пусковым фактором для развития системного воспаления [26,30].…”