Dissociation of inflammatory markers and natural killer cell activity in major depressive disorder

Abstract

Major depressive disorder is associated with increases in infectious disease risk as well as the incidence of inflammatory disorders. Declines of natural killer (NK) cell activity are reliably found in depression, whereas other studies report evidence of inflammation in depressed patients. The potential association between NK activity and circulating markers of immune activation has not been previously examined in the context of major depression. In this study, we measured levels of NK activity, circulating levels of interleukin-6 (IL-6), soluble interleukin-2 receptor, and acute phase proteins in 25 male patients with current major depressive disorder and 25 age, gender, and body weight comparable controls. As compared to controls, patients with major depressive disorder showed lower NK activity (p = .05) and higher circulating levels of IL-6 (p < .05). Levels of NK activity were not correlated with IL-6 or with other markers of immune activation. The independent effect of depression on inflammatory markers and natural killer immune responses has implications for understanding individual differences in the adverse health effects of major depressive disorder.

Introduction

Major depressive disorder, which exceeds a lifetime incidence of 10% (Kessler et al., 2003, Michaud et al., 2001), is a potent risk factor for disease morbidity with depressed persons showing a mortality rate twice that found in nondepressed persons (Penninx et al., 1999, Rudisch and Nemeroff, 2003, Wulsin et al., 1999). Altered functioning of the immune system is implicated as a mechanism that might contribute to medical morbidity of major depressive disorder including risk of infectious disease (Evans et al., 2002) as well as inflammatory disorders (Zautra et al., 2004). For example, depressed persons show reductions of cellular and innate immune responses that are associated with infectious disease susceptibility (Cohen and Miller, 2000, Leserman, 2003), whereas other studies have found that depression is linked to immune activation in patients with inflammatory disorders such as rheumatoid arthritis (Zautra et al., 2004) and cardiovascular disease (Lesperance et al., 2004, Miller et al., 2002a, Miller et al., 2002b). Indeed, several recent meta-analyses have found that major depression is reliably associated with a reduction of natural killer (NK) cell activity and with increases of circulating levels of the proinflammatory cytokine, interleukin-6 (IL-6), and possibly other markers of immune activation such as acute proteins (e.g., haptoglobin) (Herbert and Cohen, 1993, Irwin, 2002, Zorrilla et al., 2001). However, despite the number of studies that have evaluated different aspects of immunity in depression, no study has simultaneously examined the association between NK activity and inflammatory markers in the context of major depression (Raison and Miller, 2003); rather, these immune differences have been generated in separate samples of depressed patients. In this study, we evaluate levels of NK activity as well as markers of immune activation including circulating levels of IL-6, soluble interleukin-2 receptor (sIL-2R), and acute phase proteins (haptoglobin, α-1-anti-trypsin, and α-1-acid glycoprotein) in acutely depressed patients as compared to age-, gender, and body weight matched comparison controls.