Sustained Elevation of Serum Interleukin-6 and Relative Insensitivity to Hydrocortisone Differentiates Posttraumatic Stress Disorder with and Without Depression

BackgroundElevated levels of proinflammatory cytokines, especially interleukin-6 (IL-6), can mediate the greater risk for cardiovascular disease in individuals with posttraumatic stress disorder (PTSD), particularly in those with comorbid major depressive disorder (MDD). However, IL-6 levels are not consistently elevated in either PTSD or MDD. Although PTSD is associated with supersensitivity to glucocorticoids; prior studies have not evaluated the effect of comorbid MDD.MethodsSerum IL-6 levels were measured hourly between 7:00 pm and 7:00 am in individuals with PTSD with comorbid MDD (PTSD + MDD) (n = 9) and compared with those with PTSD without MDD (PTSD − MDD) (n = 9) and nontraumatized healthy control subjects (n = 14). Group differences in serum IL-6, plasma adrenocorticotropic hormone (ACTH), and plasma cortisol response to 30 mg of intravenous hydrocortisone were evaluated using linear mixed models.ResultsOnly subjects with PTSD + MDD exhibited higher, overnight serum IL-6 levels compared with individuals with PTSD − MDD (p < .01) and healthy control subjects (p < .001). Peak overnight IL-6 levels positively correlated with severity of PTSD (r = .56, p < .01) and depressive symptoms (r = .54, p < .01). Hydrocortisone administration significantly reduced IL-6 levels in both PTSD groups; however, IL-6 levels in PTSD + MDD were higher than both PTSD − MDD (p < .05) and healthy control subjects (p < .01). Following hydrocortisone administration, there was a greater reduction in levels of ACTH in PTSD − MDD compared with control subjects (p < .01).ConclusionsSustained elevations of overnight IL-6 levels and relatively decreased sensitivity to hydrocortisone distinguish PTSD + MDD from PTSD − MDD. Novel strategies that decrease IL-6 levels offer a new direction in the prevention and treatment of PTSD and associated comorbid medical illnesses.