In addition to neuroendocrine changes
PTSD pathophysiology may also involve dysfunction of the innate immune inflammatory system.
PTSD patients have been found to exhibit increased concentrations of circulating inflammatory markers such as
C-reactive protein and
interleukin-6, suggesting dysfunction of the innate immune inflammatory system. However, few studies have investigated molecular signaling pathways known to critically regulate
inflammation. Additionally, the relationship between inflammatory function and immune cell
glucocorticoid sensitivity has not been extensively explored in
PTSD. Nuclear factor-κB (NF-κB) pathway activity was examined in peripheral blood mononuclear cells obtained from 12 women with childhood abuse-related
PTSD and 24 healthy controls (ages 19-48) using
DNA-binding ELISA.
Glucocorticoid sensitivity of monocytes in whole blood was measured as the concentration of
dexamethasone needed to suppress in vitro
lipopolysaccharide-induced
tumor necrosis factor-alpha production by 50% (DEX IC(50)). Women with
PTSD displayed increased NF-κB pathway activity compared to controls (
t [34]=2.45, p=0.02) that was positively correlated with
PTSD severity (determined by
PTSD symptom severity scale) (r(s)=0.39, p=0.02). Increased NF-κB pathway activity was associated with increased whole blood monocyte DEX IC(50) (i.e. decreased sensitivity of monocytes to
glucocorticoids) across all participants (r=0.66, p<0.001). These findings suggest that enhanced inflammatory system activity in participants with childhood abuse-related
PTSD is observable at the level of NF-κB, and that in general decreased immune cell
glucocorticoid sensitivity may contribute to increased NF-κB pathway activity. Enhanced
inflammation may contribute to co-morbid somatic disease risk in persons with childhood abuse-related
PTSD.