Serum IL-7 and G-CSF in major depressive disorder Soili M. Lehto a, ⁎, Anne Huotari b,c , Leo Niskanen d , Karl-Heinz Herzig a,b,c , Tommi Tolmunen a , Heimo Viinamäki a , Heli Koivumaa-Honkanen a,e,f , Kirsi Honkalampi g , Sanna Sinikallio h , Heli Ruotsalainen c , Jukka Hintikka a a Department of Psychiatry, Kuopio University Hospital and University of Eastern Finland, 70210 Kuopio, Finland b Department of Pharmaceutics, University of Kuopio, Finland c Institute of Biomedicine, Division of Physiology and Biocenter Oulu, University of Oulu, Finland d Department of Medicine, Kuopio University Hospital and University of Eastern Finland, 70210 Kuopio, Finland e Department of Clinical Medicine, University of Oulu, Finland f Department of Psychiatry, Lapland Hospital District, 97140 Rovaniemi, Finland g Kuopio Psychiatric Center, P.O. Box 1777, 70211 Kuopio, Finland h Department of Rehabilitation, Kuopio University Hospital, Kuopio, Finland abstract article info Article history: Received 11 November 2009 Received in revised form 3 March 2010 Accepted 30 March 2010 Available online 8 April 2010 Keywords: G-CSF Growth factors IL-7 Inflammation Major depressive disorder Major depressive disorder (MDD) has been associated with dysregulated immune systems and impaired T cell function, but data on depression-related alterations in the levels of immunomodulatory growth factors are scarce. In order to further clarify the mechanisms underlying immune system dysregulation in depressed subjects, we examined the associations between MDD and serum levels of two immunomodulatory growth factors, interleukin (IL)-7 and granulocyte-colony stimulating factor (G-CSF), in 122 subjects (MDD with long-term symptomatology, n = 61; controls, n = 61). The MDD subjects had lowered levels of IL-7. In a model adjusted for age, gender and body mass index, subjects in the lowest tertile of IL-7 had a 3.4-fold increased likelihood for MDD (p = 0.010). Further adjustments for sleep disturbances, alcohol use, smoking, and metabolic syndrome did not alter these findings. Moreover, the exclusion of subjects with rheumatoid arthritis, coronary heart disease, or the use of non-steroidal anti-inflammatory medications or oral corticosteroids only slightly attenuated the findings. The G-CSF levels did not differ between the two groups. The lowering of the serum levels of IL-7, a regulator of T cell homeostasis, in MDD subjects may underlie the depression-related impaired T cell function. © 2010 Elsevier Inc. All rights reserved. 1. Introduction Enhanced low-grade inflammation has been linked to major depressive disorder (MDD) (Raison et al., 2006; Schiepers et al., 2005). However, a simultaneous impairment of T cell functions has also been reported (Irwin and Miller, 2007). Smith (1991) proposed in his macrophage theory of depression that depression is characterized by increased secretion of macrophage cytokines such as IL-1 and TNF, and suppression of the secretion of T cell-derived lymphokines. In concordance with this theory, IL-6, also a macrophage product, has been demonstrated to be elevated in depression in a recent meta- analysis (Dowlati et al., 2010). The association between depression and elevated inflammatory status is likely to be bidirectional; enhanced inflammation predisposes to depression (Gimeno et al., 2009), and depression leads to systemic inflammation (Stewart et al., 2009). A growth factor and cytokine, IL-7 is considered to be an immunostimulatory substance and a major homoeostatic cytokine (Calzascia et al., 2008). It is essential for lymphocyte development and survival (Jiang et al., 2005), and also induces the production of inflammatory cytokines from T cells (Kim et al., 2008). It additionally regulates T cell homoeostasis through (a) modulating thymic output, (b) stimulating the expansion and survival of naïve and memory T cells, and (c) inhibiting T cell apoptosis (Kim et al., 2008). Therefore, through the regulation of T cells, which secrete lymphokines, IL-7 also participates in the cascade possibly contributing to the hypothesized depression-related lymphokine suppression (Smith, 1991). However, data on the levels of IL-7 in depressed subjects are scarce. One previous Progress in Neuro-Psychopharmacology & Biological Psychiatry 34 (2010) 846–851 Abbreviations: ADS, atypical depression supplement; BDI, Beck Depression Inventory; BMI, body mass index; CNS, central nervous system; CRP, C-reactive protein; ELISA, enzyme-linked immunosorbant assay; G-CSF, granulocyte-colony stimulating factor; GM-CSF, granulocyte-macrophage colony stimulating factor; HAM-D, Hamilton depression rating scale; HDL-C, high-density lipoprotein cholesterol; HMS, high mental symptom group; IL, interleukin; KUDEP, Kuopio Depression Study; LDL-C, low-density lipoprotein cholesterol; LMS, low mental symptom group; LS, Life Satisfaction; MDD, major depressive disorder; MetS, metabolic syndrome; NSAID, non- steroidal anti-inflammatory drug; SCID, Structured Clinical Interview for DSM-IV; TAS, Toronto Alexithymia Scale; TC, total cholesterol; TG, triglycerides; Th cells, T helper cells.. ⁎ Corresponding author. Tel.: +358 40 8277 973; fax: +358 17 17 2966. E-mail address: Soili.Lehto@kuh.fi (S.M. Lehto). 0278-5846/$ – see front matter © 2010 Elsevier Inc. All rights reserved. doi:10.1016/j.pnpbp.2010.03.033 Contents lists available at ScienceDirect Progress in Neuro-Psychopharmacology & Biological Psychiatry journal homepage: www.elsevier.com/locate/pnp