Monocytes from Depressed Patients Display an Altered Pattern of Response to Endotoxin Challenge

Abstract

It is now well established that major depression is accompanied and characterized by altered responses of the immune-inflammatory system. In this study we investigated the pro-inflammatory activation of monocytes isolated from depressed patients as a parameter not influenced by such confounds as the time of day, the nutritional and exercise status or the age and gender of patients. Monocytes from depressed patients and from healthy controls were isolated in vitro; after 24-h incubation under basal conditions, cells were exposed for 24-h to 100 ng/ml of endotoxin (bacterial lipopolysaccharide, LPS). We found that monocytes from drug-free depressed patients and controls release the same amounts of prostaglandin E2 (PGE2) under basal conditions, whereas monocytes from patients are dramatically less reactive to LPS (8.62-fold increase vs previous 24 hrs) compared to healthy controls (123.3-fold increase vs previous 24 hrs). Such blunted prostanoid production was paralleled by a reduction in COX-2 gene expression, whereas other pro-inflammatory mediators, namely interleukin-1β (IL-1 β) and -6 (IL-6) showed a trend to increased gene expression. The above changes were not associated to increased levels of circulating glucocorticoids. After 8 months of antidepressive drug treatment, the increase in PGE2 production after the endotoxin challenge was partially restored, whereas the increase in IL-1 β and -6 levels observed at baseline was completely abolished. In conclusion, our findings show that the reactivity of monocytes from depressed patients might be considered as a marker of the immune-inflammatory disorders associated to depression, although the lack of paired healthy controls at follow-up does not allow to conclude that monocyte reactivity to endotoxin is also a marker of treatment outcome.

Glucocorticoid mediated regulation of inflammation in human monocytes is associated with depressive mood and obesity

“…Also, LPS-stimulated monocytes from depressed patients produced greater amounts of IL-6 and IL-1β but less prostaglandin E2, highlighting diverse regulatory pathways of inflammatory monocyte reactivity that may be impaired in depression (Lisi et al, 2013). These discrepancies in findings between these previous and our studies are likely due to differences in the immunological outcomes and methods of cellular investigations.…”

Neuroimmune and neuroendocrine abnormalities in depression: two sides of the same coin

“…We have recently conducted a systematic review and meta‐analysis to examine this prediction in the clinical literature (unpublished). Despite the number of studies that have examined biological disturbances in depressed patients, including large numbers that have measured either endocrine or innate immune variables, only eight studies have examined both systems in the same group of patients in any detail (involving a measurement of innate immune function, cortisol levels, and GR resistance) . In these depressed groups, increased levels of proinflammatory cytokines and an increased incidence of glucocorticoid resistance were more common findings than increased levels of cortisol.…”

Absolute Measurements of Macrophage Migration Inhibitory Factor and Interleukin-1-β mRNA Levels Accurately Predict Treatment Response in Depressed Patients

“…While depressed patients in general tend to show higher blood levels of inflammatory biomarkers compared with controls (Howren et al, 2009;Martinez et al, 2012), depressed patients who are resistant to conventional antidepressants tend to have even higher concentrations of these biomarkers, both as plasma/serum proteins (Sluzewska et al, 1997; Lanquillon et al, 2000; Fitzgerald et al, 2006; Rethorst et al, 2013) and as blood mRNA levels (Carvalho et al, 2013; Cattaneo et al, 2013; Lisi et al, 2013; Powell et al, 2013). However, despite this large amount of evidence, none of these findings have been translated yet into clinical practice, partly because different studies use different biomarkers, often measured with assays that are laboratory specific.…”