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Activitas Nervosa Superior 2010; 52 : 2,76-81 76 M ETA - ANALYSIS OF P LASMA I NTERLEUKINE -6 L EVELS IN P ATIENTS WITH D EPRESSIVE D ISORDER Gustav Bizik * Center for Neuropsychiatric Research of Traumatic Stress, Department of Psychiatry, 1 st Faculty of Medicine, Charles University, Prague, Czech Republic Received March 15, 2010; accepted April 10, 2010 Abstract Growing body of evidence suggests that inflammatory processes play an important role in the pathophysiology and the clinical course of depressive disorder, as well as several others major psychiatric and somatic conditions. Interleukin (IL- 6), one of the proinflammatory cytokine, has been extensively examined in a number of studies among depressed pa- tients. To assess quantitatively the relationship between depression and IL-6, a systematic review of relevant literature published to October 2009 was performed and relevant data were meta-analysed using random-effects model. A positive association was found (standardized difference in means=1.055, p>0,001), although a significant heterogeneity among studies (Q(15)=141, p<0,001) points to relevance of further subgroup analyses. Key words: Depression; IL-6; Meta-analysis INTRODUCTION Increasing body of research has been focused on implications of immune mechanisms in patho- physiological pathways leading to major somatic and psychiatric conditions. Importantly, proinflammatory processe frequently indexed using elevated levels of proinflammatory cytokines (such as interleukin IL-1β, IL-6, interferon IFN-γ, tumor necrosis factor TNF-α) have been reported in physical conditions such as in metabolic syndrome (Shelton & Miller, 2010), atherosclerosis (Libby, Ridker, & Maseri, 2002) and cancer (Hodge, Hurt, & Farrar, 2005; Nilsson, Langley, & Fidler, 2005) and psychiatric conditions such as depressive disorder (Howren, Lamkin, & Suls, 2009), schizophrenia (Potvin et al., 2008) and posttraumatic stress disorder (PTSD) (Baker et al., 2001; Gill, Vythilingam, & Page, 2008; Hoge et al., 2009; Maes et al., 1999; Song, Zhou, Guan, & Wang, 2007). Although the question of directionality (from psychiatric condition towards inflammation or vice versa) is rather complex and remain open (Stewart, Rand, Muldoon, & Kamarck, 2009), inflammatory processes have been proposed to explain in part significant association between psychiatric and somatic morbidity. Of note, proinflammatory cytokines, together with stress hormones, represent primary mediators of adversive health effects related to prolonged and dysregulated stress response in allostatic load model (Juster, McEwen, & Lupien, 2009). Due to its particular role in brain-body interactions, IL- 6 has been among the most extensively investigated proinflammatory molecule in a range of pre-clinical and clinical protocols. Its effects are multifaceted with an important role in the regulation of the innate immune reactions and complex interactions with stress system responses and neurotransmitter systems. In periphery, it
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