Skip to main content Accessibility help

Interleukin-6, C-reactive protein and interleukin-10 after antidepressant treatment in people with depression: a meta-analysis

Published online by Cambridge University Press:  16 February 2012

S. A. Hiles
Centre for Brain and Mental Health Research, Faculty of Health, University of Newcastle, New South Wales, Australia
A. L. Baker
Centre for Brain and Mental Health Research, Faculty of Health, University of Newcastle, New South Wales, Australia
T. de Malmanche
Immunology, Hunter Area Pathology Service, John Hunter Hospital, New South Wales, Australia
J. Attia
Centre for Clinical Epidemiology and Biostatistics, Faculty of Health, University of Newcastle, New South Wales, Australia Hunter Medical Research Institute, John Hunter Hospital, New South Wales, Australia
E-mail address:



Cross-sectional studies support an association between depression and inflammatory markers. However, little is known of their relationship in the context of antidepressant treatment. Our aim was to explore via meta-analysis whether antidepressant treatment is associated with a reduction in three inflammatory markers associated with depression.


A computerized search of EMBASE, Medline, PsycINFO and Cochrane Library databases was completed using subject headings for depression and either interleukin-6, C-reactive protein or interleukin-10, selecting studies which reported circulating levels of inflammatory markers before and after antidepressant treatment for people with depression. Outcome and moderator variables were coded for analysis, including inflammatory marker change, depression severity change, age, gender ratio, assay brand, treatment response and weight change.


Pooled effect sizes showed a significant decrease in interleukin-6 (n=14, d=−0.42, p=0.02), marginally significant decrease in C-reactive protein (n=8, d=−0.57, p=0.05) and a non-significant decrease in interleukin-10 (n=3, d=−0.45, p=0.14) after treatment. High levels of heterogeneity were observed, which may be associated with clinical variations between the studies such as weight gain, anxiety, incomplete remission and other individual differences and co-morbidities.


The findings of this meta-analysis indicate that there may be a normalization of overactive inflammatory processes following antidepressant treatment.

Review Article
Copyright © Cambridge University Press 2012

Access options

Get access to the full version of this content by using one of the access options below.


Basterzi, AD, Aydemir, C, Kisa, C, Aksaray, S, Tuzer, V, Yazici, K, Goka, E (2005). IL-6 levels decrease with SSRI treatment in patients with major depression. Human Psychopharmacology 20, 473476.CrossRefGoogle ScholarPubMed
Bland, JM, Altman, DG (1994). Statistics notes: some examples of regression towards the mean. British Medical Journal 309, 780.CrossRefGoogle Scholar
Borenstein, M, Hedges, LV, Higgins, JPT, Rothstein, HR (2009). Introduction to Meta-analysis. John Wiley & Sons: Chichester, UK.CrossRefGoogle Scholar
Bossola, M, Ciciarelli, C, Di Stasio, E, Conte, GL, Vulpio, C, Luciani, G, Tazza, L (2010). Correlates of symptoms of depression and anxiety in chronic hemodialysis patients. General Hospital Psychiatry 32, 125131.CrossRefGoogle ScholarPubMed
Carvalho, LA, Garner, BA, Dew, T, Fazakerley, H, Pariante, CM (2010). Antidepressants, but not antipsychotics, modulate GR function in human whole blood: an insight into molecular mechanisms. European Neuropsychopharmacology 20, 379387.CrossRefGoogle ScholarPubMed
Carvalho, LA, Pariante, CM (2008). In vitro modulation of the glucocorticoid receptor by antidepressants. Stress: The International Journal on the Biology of Stress 11, 411424.CrossRefGoogle ScholarPubMed
Chen, Y-C, Lin, W-W, Chen, Y-J, Mao, W-C, Hung, Y-J (2010). Antidepressant effects on insulin sensitivity and proinflammatory cytokines in the depressed males. Mediators of Inflammation. Published online: 18 May 2010. doi:10.1155/2010/573594.CrossRefGoogle ScholarPubMed
Dawood, T, Lambert, EA, Barton, DA, Laude, D, Elghozi, JL, Esler, MD, Haikerwal, D, Kaye, DM, Hotchkin, EJ, Lambert, GW (2007). Specific serotonin reuptake inhibition in major depressive disorder adversely affects novel markers of cardiac risk. Hypertension Research 30, 285293.CrossRefGoogle ScholarPubMed
Dowlati, Y, Herrmann, N, Swardfager, W, Liu, H, Sham, L, Reim, EK, Lanctôt, KL (2010). A meta-analysis of cytokines in major depression. Biological Psychiatry 67, 446457.CrossRefGoogle ScholarPubMed
Egger, M, Davey Smith, G, Schneider, M, Minder, C (1997). Bias in meta-analysis detected by a simple, graphical test. British Medical Journal 315, 629634.CrossRefGoogle ScholarPubMed
Evans, DL, Charney, DS, Lewis, L, Golden, RN, Gorman, JM, Krishnan, KRR, Nemeroff, CB, Bremner, JD, Carney, RM, Coyne, JC, Delong, MR, Frasure-Smith, N, Glassman, AH, Gold, PW, Grant, I, Gwyther, L, Ironson, G, Johnson, RL, Kanner, AM, Katon, WJ, Kaufmann, PG, Keefe, FJ, Ketter, T, Laughren, TP, Leserman, J, Lyketsos, CG, McDonald, WM, McEwen, BS, Miller, AH, Musselman, D, O'Connor, C, Petitto, JM, Pollock, BG, Robinson, RG, Roose, SP, Rowland, J, Sheline, Y, Sheps, DS, Simon, G, Spiegel, D, Stunkard, A, Sunderland, T, Tibbits, JP, Valvo, WJ (2005). Mood disorders in the medically ill: scientific review and recommendations. Biological Psychiatry 58, 175189.CrossRefGoogle ScholarPubMed
Fornaro, M, Martino, M, Battaglia, F, Colicchio, S, Perugi, G (2011). Increase in IL-6 levels among major depressive disorder patients after a 6-week treatment with duloxetine 60 mg/day: a preliminary observation. Neuropsychiatric Disease and Treatment 7, 5156.CrossRefGoogle ScholarPubMed
Gabay, C, Kushner, I (1999). Acute-phase proteins and other systemic responses to inflammation. New England Journal of Medicine 340, 448454.CrossRefGoogle ScholarPubMed
Hernandez, ME, Mendieta, D, Martinez-Fong, D, Loria, F, Moreno, J, Estrada, I, Bojalil, R, Pavon, L (2008). Variations in circulating cytokine levels during 52 week course of treatment with SSRI for major depressive disorder. European Neuropsychopharmacology 18, 917924.CrossRefGoogle ScholarPubMed
Higgins, JPT, Thompson, SG, Deeks, JJ, Altman, DG (2003). Measuring inconsistency in meta-analyses. British Medical Journal 327, 557560.CrossRefGoogle ScholarPubMed
Howren, MB, Lamkin, DM, Suls, J (2009). Associations of depression with C-reactive protein, IL-1, and IL-6: a meta-analysis. Psychosomatic Medicine 71, 171186.CrossRefGoogle ScholarPubMed
Irwin, MR, Miller, AH (2007). Depressive disorders and immunity: 20 years of progress and discovery. Brain, Behavior, and Immunity 21, 374383.CrossRefGoogle ScholarPubMed
Janssen, DGA, Caniato, RN, Verster, JC, Baune, BT (2010). A psychoneuroimmunological review on cytokines involved in antidepressant treatment response. Human Psychopharmacology 25, 201215.CrossRefGoogle ScholarPubMed
Jazayeri, S, Keshavarz, SA, Tehrani-Doost, M, Djalali, M, Hosseini, M, Amini, H, Chamari, M, Djazayery, A (2010). Effects of eicosapentaenoic acid and fluoxetine on plasma cortisol, serum interleukin-1beta and interleukin-6 concentrations in patients with major depressive disorder. Psychiatry Research 178, 112115.CrossRefGoogle ScholarPubMed
Kagaya, A, Kugaya, A, Takebayashi, M, Fukue-Saeki, M, Saeki, T, Yamawaki, S, Uchitomi, Y (2001). Plasma concentrations of interleukin-1beta, interleukin-6, soluble interleukin-2 receptor and tumor necrosis factor alpha of depressed patients in Japan. Neuropsychobiology 43, 5962.CrossRefGoogle ScholarPubMed
Kenis, G, Maes, M (2002). Effects of antidepressants on the production of cytokines. International Journal of Neuropsychopharmacology 5, 401–142.CrossRefGoogle ScholarPubMed
Khan, AMD, Brodhead, AEMS, Schwartz, KAMS, Kolts, RLP, Brown, WAMD (2005). Sex differences in antidepressant response in recent antidepressant clinical trials. Journal of Clinical Psychopharmacology 25, 318324.CrossRefGoogle ScholarPubMed
Kubera, M, Kenis, G, Bosmans, E, Zieba, A, Dudek, D, Nowak, G, Maes, M (2000). Plasma levels of interleukin-6, interleukin-10, and interleukin-1 receptor antagonist in depression: comparison between the acute state and after remission. Polish Journal of Pharmacology 52, 237241.Google ScholarPubMed
Lanquillon, S, Krieg, JC, Bening-Abu-Shach, U, Vedder, H (2000). Cytokine production and treatment response in major depressive disorder. Neuropsychopharmacology 22, 370379.CrossRefGoogle ScholarPubMed
Leo, R, Di Lorenzo, G, Tesauro, M, Razzini, C, Forleo, GB, Chiricolo, G, Cola, C, Zanasi, M, Troisi, A, Siracusano, A, Lauro, R, Romeo, F (2006). Association between enhanced soluble CD40 ligand and proinflammatory and prothrombotic states in major depressive disorder: pilot observations on the effects of selective serotonin reuptake inhibitor therapy. Journal of Clinical Psychiatry 67, 17601766.CrossRefGoogle ScholarPubMed
Lindqvist, D, Janelidze, S, Hagell, P, Erhardt, S, Samuelsson, M, Minthon, L, Hansson, O, Bjorkqvist, M, Traskman-Bendz, L, Brundin, L (2009). Interleukin-6 is elevated in the cerebrospinal fluid of suicide attempters and related to symptom severity. Biological Psychiatry 66, 287292.CrossRefGoogle ScholarPubMed
Mackay, GM, Forrest, CM, Christofides, J, Bridel, MA, Mitchell, S, Cowlard, R, Stone, TW, Darlington, LG (2009). Kynurenine metabolites and inflammation markers in depressed patients treated with fluoxetine or counselling. Clinical and Experimental Pharmacology and Physiology 36, 425435.CrossRefGoogle ScholarPubMed
Maes, M (2001). The immunoregulatory effects of antidepressants. Human Psychopharmacology: Clinical and Experimental 16, 95103.CrossRefGoogle ScholarPubMed
Maes, M, Bosmans, E, De Jongh, R, Kenis, G, Vandoolaeghe, E, Neels, H (1997). Increased serum IL-6 and IL-1 receptor antagonist concentrations in major depression and treatment resistant depression. Cytokine 9, 853858.CrossRefGoogle ScholarPubMed
Maes, M, Meltzer, HY, Bosmans, E, Bergmans, R, Vandoolaeghe, E, Ranjan, R, Desnyder, R (1995). Increased plasma concentrations of interleukin-6, soluble interleukin-6, soluble interleukin-2 and transferrin receptor in major depression. Journal of Affective Disorders 34, 301309.CrossRefGoogle ScholarPubMed
Maes, M, Yirmyia, R, Noraberg, J, Brene, S, Hibbeln, J, Perini, G, Kubera, M, Bob, P, Lerer, B, Maj, M (2009). The inflammatory and neurodegenerative hypothesis of depression: leads for future research and new drug developments in depression. Metabolic Brain Disease 24, 2753.CrossRefGoogle ScholarPubMed
Mikova, O, Yakimova, R, Bosmans, E, Kenis, G, Maes, M (2001). Increased serum tumor necrosis factor alpha concentrations in major depression and multiple sclerosis. European Neuropsychopharmacology 11, 203208.CrossRefGoogle ScholarPubMed
Miller, AH, Maletic, V, Raison, CL (2009). Inflammation and its discontents: the role of cytokines in the pathophysiology of major depression. Biological Psychiatry 65, 732741.CrossRefGoogle ScholarPubMed
Moore, KW, de Waal Malefyt, R, Coffman, RL, O'Garra, A (2001). Interleukin-10 and the interleukin-10 receptor. Annual Review of Immunology 19, 683765.CrossRefGoogle ScholarPubMed
O'Brien, SM, Scott, LV, Dinan, TG (2006). Antidepressant therapy and C-reactive protein levels. British Journal of Psychiatry 188, 449452.CrossRefGoogle ScholarPubMed
O'Donovan, A, Hughes, BM, Slavich, GM, Lynch, L, Cronin, M-T, O'Farrelly, C, Malone, KM (2010). Clinical anxiety, cortisol and interleukin-6: evidence for specificity in emotion-biology relationships. Brain, Behavior, and Immunity 24, 10741077.CrossRefGoogle ScholarPubMed
Park, HS, Park, JY, Yu, R (2005). Relationship of obesity and visceral adiposity with serum concentrations of CRP, TNF-α and IL-6. Diabetes Research and Clinical Practice 69, 2935.CrossRefGoogle ScholarPubMed
Pizzi, C, Mancini, S, Angeloni, L, Fontana, F, Manzoli, L, Costa, GM (2009). Effects of selective serotonin reuptake inhibitor therapy on endothelial function and inflammatory markers in patients with coronary heart disease. Clinical Pharmacology & Therapeutics 86, 527–32.CrossRefGoogle ScholarPubMed
Pudar Hozo, S, Djulbegovic, B, Hozo, I (2005). Estimating the mean and variance from the median, range, and the size of a sample. BMC Medical Research Methodology 5(13).Google Scholar
Rosenthal, R (1979). The file drawer problem and tolerance for null results. Psychological Bulletin 86, 638641.CrossRefGoogle Scholar
Rothermundt, M, Arolt, V, Fenker, J, Gutbrodt, H, Peters, M, Kirchner, H (2001). Different immune patterns in melancholic and non-melancholic major depression. European Archives of Psychiatry and Clinical Neuroscience 251, 9097.CrossRefGoogle ScholarPubMed
Rush, AJ, Zimmerman, M, Wisniewski, SR, Fava, M, Hollon, SD, Warden, D, Biggs, MM, Shores-Wilson, K, Shelton, RC, Luther, JF, Thomas, B, Trivedi, MH (2005). Comorbid psychiatric disorders in depressed outpatients: demographic and clinical features. Journal of Affective Disorders 87, 4355.CrossRefGoogle ScholarPubMed
Serretti, A, Mandelli, L (2010). Antidepressants and body weight: a comprehensive review and meta-analysis. Journal of Clinical Psychiatry 71, 12591272.CrossRefGoogle ScholarPubMed
Sluzewska, A, Rybakowski, JK, Laciak, M, Mackiewicz, A, Sobieska, M, Wiktorowicz, K (1995). Interleukin-6 serum levels in depressed patients before and after treatment with fluoxetine. Annals of the New York Academy of Sciences 762, 474476.CrossRefGoogle ScholarPubMed
Sluzewska, A, Sobieska, M, Rybakowski, JK (1997). Changes in acute-phase proteins during lithium potentiation of antidepressants in refractory depression. Neuropsychobiology 35, 123127.CrossRefGoogle ScholarPubMed
Song, C, Halbreich, U, Han, C, Leonard, BE, Luo, H (2009). Imbalance between pro- and anti-inflammatory cytokines, and between Th1 and Th2 cytokines in depressed patients: the effect of electroacupuncture or fluoxetine treatment. Pharmacopsychiatry 42, 182188.CrossRefGoogle ScholarPubMed
Tuglu, C, Kara, SH, Caliyurt, O, Vardar, E, Abay, E (2003). Increased serum tumor necrosis factor-alpha levels and treatment response in major depressive disorder. Psychopharmacology 170, 429433.CrossRefGoogle ScholarPubMed
Tummers, B, van der Laan, J, Huyser, K (2008). Data Thief III, v. 1.5, computer software ( Accessed 8 September 2010.Google Scholar
Yao, H, Tao, L-G, Zhang, X-B, Sha, W-W, Hou, G, Zhang, Z-J (2004). Variety of cell-mediated immunity and the metabolic products of monoamine neural transmitter in depression patients before and after therapy. Chinese Journal of Clinical Rehabilitation 8, 29782979.Google Scholar
Yoshimura, R, Hori, H, Ikenouchi-Sugita, A, Umene-Nakano, W, Ueda, N, Nakamura, J (2009). Higher plasma interleukin-6 (IL-6) level is associated with SSRI- or SNRI-refractory depression. Progress in Neuro-Psychopharmacology and Biological Psychiatry 33, 722726.CrossRefGoogle ScholarPubMed
Zorrilla, EP, Luborsky, L, McKay, JR, Rosenthal, R, Houldin, A, Tax, A, McCorkle, R, Seligman, DA, Schmidt, K (2001). The relationship of depression and stressors to immunological assays: a meta-analytic review. Brain, Behavior and Immunity 15, 199226.CrossRefGoogle ScholarPubMed

Hiles Supplementary Material

Table S1.doc

File 126 KB

Altmetric attention score

Full text views

Full text views reflects PDF downloads, PDFs sent to Google Drive, Dropbox and Kindle and HTML full text views.

Total number of HTML views: 59
Total number of PDF views: 311 *
View data table for this chart

* Views captured on Cambridge Core between September 2016 - 20th January 2021. This data will be updated every 24 hours.

Hostname: page-component-76cb886bbf-cdxmh Total loading time: 0.601 Render date: 2021-01-20T01:45:48.133Z Query parameters: { "hasAccess": "0", "openAccess": "0", "isLogged": "0", "lang": "en" } Feature Flags: { "shouldUseShareProductTool": true, "shouldUseHypothesis": true, "isUnsiloEnabled": true, "metricsAbstractViews": false, "figures": false, "newCiteModal": false }

Send article to Kindle

To send this article to your Kindle, first ensure is added to your Approved Personal Document E-mail List under your Personal Document Settings on the Manage Your Content and Devices page of your Amazon account. Then enter the ‘name’ part of your Kindle email address below. Find out more about sending to your Kindle. Find out more about sending to your Kindle.

Note you can select to send to either the or variations. ‘’ emails are free but can only be sent to your device when it is connected to wi-fi. ‘’ emails can be delivered even when you are not connected to wi-fi, but note that service fees apply.

Find out more about the Kindle Personal Document Service.

Interleukin-6, C-reactive protein and interleukin-10 after antidepressant treatment in people with depression: a meta-analysis
Available formats

Send article to Dropbox

To send this article to your Dropbox account, please select one or more formats and confirm that you agree to abide by our usage policies. If this is the first time you use this feature, you will be asked to authorise Cambridge Core to connect with your <service> account. Find out more about sending content to Dropbox.

Interleukin-6, C-reactive protein and interleukin-10 after antidepressant treatment in people with depression: a meta-analysis
Available formats

Send article to Google Drive

To send this article to your Google Drive account, please select one or more formats and confirm that you agree to abide by our usage policies. If this is the first time you use this feature, you will be asked to authorise Cambridge Core to connect with your <service> account. Find out more about sending content to Google Drive.

Interleukin-6, C-reactive protein and interleukin-10 after antidepressant treatment in people with depression: a meta-analysis
Available formats

Reply to: Submit a response

Your details

Conflicting interests

Do you have any conflicting interests? *