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Cytokines in Depression and Heart Failure

From the Department of Psychiatry and Behavioral Sciences (J.P., M.D.S.) and Division of Cardiology, Department of Medicine (W.C.L.), University of Washington, Seattle, Washington.

Address reprint requests to: Jagoda Pasic, MD, PhD, Department of Psychiatry and Behavioral Sciences, Box 356560, Seattle, WA 98195-6560. Email: jpasic{at}u.washington.edu

ABSTRACT

OBJECTIVE: There is a convincing body of evidence linking depression, cardiovascular disease, and mortality. There is also growing evidence that depression is a risk factor for congestive heart failure (CHF) and that CHF patients with major depression have higher rates of mortality and repeat hospitalizations. Currently there are no proposed neurobiological or neuroimmune mechanisms for the comorbidity of heart failure and depression.

METHODS: This review focuses on the recent literature about the role of cytokines in CHF and depression as separate conditions. This review also attempts to identify the overlapping immunological mechanisms that have a potential for future research in the pathophysiology of comorbid depression and CHF.

RESULTS: Results of current studies suggest that cytokines exert deleterious effects on the heart and that soluble tumor necrosis factor (TNF) receptor 2 leads to reversal of the cardiotoxic effects of TNF, although the clinical significance of this is unclear. Major depression has been associated with alteration of various aspects of the innate immune system, including cellular components (such as microphages, neutrophils, and natural killer cells) and soluble mediators (such as acute-phase reaction proteins and cytokines). It is inconclusive whether antidepressants have immunoregulatory effects.

CONCLUSIONS: The literature has not yet addressed the role of cytokines in comorbid depression and CHF. But cytokines may provide a new avenue in understanding brain-body interaction in depression and heart failure.

Key Words: major depression, • congestive heart failure, • comorbidity, • pathophysiology, • immunomodulation, • cytokines.

Abbreviations: CHF = congestive heart failure;; CRH = corticotropin-releasing hormone;; HPA = hypothalamic-pituitary-adrenal;; IHD = ischemic heart disease;; IL = interleukin;; INF = interferon;; LV = left ventricular;; mRNA = messenger ribonucleic acid;; NK = natural killer;; NYHA = New York Heart Association;; OR = odds ratio;; s = soluble;; TNF = tumor necrosis factor;; TNFR = tumor necrosis factor receptor;; 5-HT = 5-hydroxytryptamine (serotonin).

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