The role of inflammation and the immune system in depression has been extensively studied. The evidence supporting this link has been showed in numerous studies over the past ten years. Nationwide studies and meta-analyses of smaller cohort studies have uncovered a correlation between pre-existing inflammatory conditions such as type 1 diabetes, rheumatoid arthritis (RA), or hepatitis, and an increased risk of depression. Data also shows that using pro-inflammatory agents in the treatment of diseases like melanoma can lead to depression. Several meta-analytical studies have found increased levels of proinflammatory cytokines and chemokines in depressed patients.[1] This link has led scientists to investigate the effects of antidepressants on the immune system.
SSRIs were originally invented with the goal of increasing levels of available serotonin in the extracellular spaces. However, the delayed response between when patients first begin SSRI treatment to when they see effects has led scientists to believe that other molecules are involved in the efficacy of these drugs.[2] To investigate the apparent anti-inflammatory effects of SSRIs, both Kohler et al. and Więdłocha et al. conducted meta-analyses which have shown that after antidepressant treatment the levels of cytokines associated with inflammation are decreased.[3][4] A large cohort study conducted by researchers in the Netherlands investigated the association between depressive disorders, symptoms, and antidepressants with inflammation. The study showed decreased levels of interleukin (IL)-6, a cytokine that has proinflammatory effects, in patients taking SSRIs compared to non-medicated patients.[5]
Treatment with SSRIs has shown reduced production of inflammatory cytokines such as IL-1β, tumor necrosis factor (TNF)-α, IL-6, and interferon (IFN)-γ, which leads to a decrease in inflammation levels and subsequently a decrease in the activation level of the immune response. [6] These inflammatory cytokines have been shown to activate microglia which are specialized macrophages that reside in the brain. Macrophages are a subset of immune cells responsible for host defense in the innate immune system. Macrophages can release cytokines and other chemicals to cause an inflammatory response. Peripheral inflammation can induce an inflammatory response in microglia and can cause neuroinflammation. SSRIs inhibit proinflammatory cytokine production which leads to less activation of microglia and peripheral macrophages. SSRIs not only inhibit the production of these proinflammatory cytokines, they also have been shown to upregulate anti-inflammatory cytokines such as IL-10. Taken together, this reduces the overall inflammatory immune response. [6] [7]
In addition to affecting cytokine production, there is evidence that treatment with SSRIs has effects on the proliferation and viability of immune system cells involved in both innate and adaptive immunity. Evidence shows that SSRIs can inhibit proliferation in T-cells, which are important cells for adaptive immunity and can induce inflammation. SSRIs can also induce apoptosis, programmed cell death, in T-cells. The full mechanism of action for the anti-inflammatory effects of SSRIs is not fully known. However, there is evidence for various pathways to have a hand in the mechanism. One such possible mechanism is the increased levels of cyclic adenosine monophosphate (cAMP) as a result of interference with activation of protein kinase A (PKA), a cAMP dependent protein. Other possible pathways include interference with calcium ion channels, or inducing cell death pathways like MAPK.[8]
The anti-inflammatory effects of SSRIs have prompted studies of the efficacy of SSRIs in the treatment of autoimmune diseases such as multiple sclerosis, RA, inflammatory bowel diseases, and septic shock. These studies have been performed in animal models but have shown consistent immune regulatory effects. Fluoxetine, an SSRI, has also shown efficacy in animal models of graft vs. host disease.[8] SSRIs have also been used successfully as pain relievers in patients undergoing oncology treatment. The effectiveness of this has been hypothesized to be at least in part due to the anti-inflammatory effects of SSRIs.[7]
Article Evaluation T helper 17 cell
editInformation is relevant to Th17 cells without any distracting tangents.
-Very limited article, large section on Th17 role in HIV without much specific information on other roles of Th17 cells
-Introduction is concise and clear but lacks citations. Links to other pages are good.
- Good citations for most information, citation needed for one or two facts
-Draws a conclusion in HIV section paragraph 1
-Lacks supporting evidence or detail for most of the article.
-Citation links work and are all from reputable peer-reviewed journals
-Good cursory introduction to Th17 cells but requires more information on specific functions as well as clearer evidence and citations to support facts.
 | This is a user sandbox of Alexandracassano. You can use it for testing or practicing edits. This is not the sandbox where you should draft your assigned article for a dashboard.wikiedu.org course. To find the right sandbox for your assignment, visit your Dashboard course page and follow the Sandbox Draft link for your assigned article in the My Articles section. |
| | This is a user sandbox of Alexandracassano. You can use it for testing or practicing edits. This is not the sandbox where you should draft your assigned article for a dashboard.wikiedu.org course. To find the right sandbox for your assignment, visit your Dashboard course page and follow the Sandbox Draft link for your assigned article in the My Articles section. |
- ^ Kohler, Ole; Krogh, Jesper; Mors, Ole; Eriksen Benros, Michael (26 August 2016). "Inflammation in Depression and the Potential for Anti-Inflammatory Treatment". Current Neuropharmacology. 14 (7): 732–742. doi:10.2174/1570159X14666151208113700.
- ^ Köhler, Stephan; Cierpinsky, Katharina; Kronenberg, Golo; Adli, Mazda (January 2016). "The serotonergic system in the neurobiology of depression: Relevance for novel antidepressants". Journal of Psychopharmacology. 30 (1): 13–22. doi:10.1177/0269881115609072.
- ^ Köhler, Cristiano A.; Freitas, Thiago H.; Stubbs, Brendon; Maes, Michael; Solmi, Marco; Veronese, Nicola; de Andrade, Nayanna Q.; Morris, Gerwyn; Fernandes, Brisa S.; Brunoni, André R.; Herrmann, Nathan; Raison, Charles L.; Miller, Brian J.; Lanctôt, Krista L.; Carvalho, André F. (13 June 2017). "Peripheral Alterations in Cytokine and Chemokine Levels After Antidepressant Drug Treatment for Major Depressive Disorder: Systematic Review and Meta-Analysis". Molecular Neurobiology. doi:10.1007/s12035-017-0632-1.
- ^ Więdłocha, Magdalena; Marcinowicz, Piotr; Krupa, Renata; Janoska-Jaździk, Marlena; Janus, Marta; Dębowska, Weronika; Mosiołek, Anna; Waszkiewicz, Napoleon; Szulc, Agata (April 2017). "Effect of antidepressant treatment on peripheral inflammation markers – A meta-analysis". Progress in Neuro-Psychopharmacology and Biological Psychiatry. doi:10.1016/j.pnpbp.2017.04.026.
- ^ Vogelzangs, N; Duivis, H E; Beekman, A T F; Kluft, C; Neuteboom, J; Hoogendijk, W; Smit, J H; de Jonge, P; Penninx, B W J H (February 2012). "Association of depressive disorders, depression characteristics and antidepressant medication with inflammation". Translational Psychiatry. 2 (2): e79. doi:10.1038/tp.2012.8.
- ^ a b Kalkman, Hans O.; Feuerbach, Dominik (July 2016). "Antidepressant therapies inhibit inflammation and microglial M1-polarization". Pharmacology & Therapeutics. 163: 82–93. doi:10.1016/j.pharmthera.2016.04.001.
- ^ a b Nazimek, Katarzyna; Strobel, Spencer; Bryniarski, Paweł; Kozlowski, Michael; Filipczak-Bryniarska, Iwona; Bryniarski, Krzysztof (June 2017). "The role of macrophages in anti-inflammatory activity of antidepressant drugs". Immunobiology. 222 (6): 823–830. doi:10.1016/j.imbio.2016.07.001.
- ^ a b Gobin, Veerle; Van Steendam, Katleen; Denys, Damiaan; Deforce, Dieter (May 2014). "Selective serotonin reuptake inhibitors as a novel class of immunosuppressants". International Immunopharmacology. 20 (1): 148–156. doi:10.1016/j.intimp.2014.02.030.