Inflammation and immune system dysfunction

What is inflammation and the immune system?

Inflammation is caused by the immune system’s response to pathogens or tissue damage. The immune system is the body’s first line of defense and predominantly uses proteins called cytokines that are secreted by immune cells and act to allow cell-to-cell communication. Cytokines have influence over many cell types, including T helper lymphocytes (Th cells, or white blood cells). There are two types of Th cells, Th1 and Th2, which have different functions in the body’s defense against infection. Cytokines act to regulate immunological and inflammatory responses to pathogens and are understood to function as intermediaries between the immune system and the central nervous system (CNS). C-reactive protein (CRP) is released by the body during inflammation. Increased CRP blood levels are not only suggestive of infection, but also chronic inflammatory conditions, including cardiovascular disease, diabetes, and metabolic dysfunction.

Cytokines include interleukins (IL), interferons (IFN), tumor necrosis factors (TNF), transforming growth factors (TGF), and chemokines. These molecules are synthesised and secreted by a variety of cell types, including not only immune cells such as T lymphocytes, natural killer (NK) cells, dendritic cells, polymorphonuclear leukocytes, monocytes/macrophages, and microglia, as well as non-immune cells, such as fibroblasts, endothelial cells, adipocytes, and neurons. Alterations of these immune-system mediators could have widespread effects for immune system functioning.

What is the evidence for inflammation and immune system anomalies in bipolar disorder?

Moderate to high quality evidence suggests large effects of increased CRP levels in people with bipolar disorder during a manic phase and medium-sized effects during depression or euthymia, when compared to controls without bipolar disorder. The effects increased slightly in studies that matched controls for age and BMI (depression and euthymia only), in studies of drug-free patients (depression only) and in studies using serum rather than plasma measures (mania only). The effects were not related to symptom severity, but were decreased slightly after resolution of the index mood episode.

Moderate to high quality evidence also suggests medium-sized effects of increased neutrophil/lymphocyte ratio (NLR) and platelet/lymphocyte ratio (PLR) levels in people with bipolar disorder (in any mood phase). The effects were similar during manic phases, and not significant during euthymic phases. No studies reported results separately for depression phases. Increasing age and male gender were associated with larger effect sizes for NLR but not PLR.

Similar quality evidence suggests small to medium-sized effects of increased IL-4, IL-10. sIL-2R, sIL-6R, TNF-a and sTNFR1 in serum or plasma of people with bipolar disorder compared to controls. Small, trend effects were found for IL-1b and IL-6, and no effects were found for IL-2, IFN-y, C-C motif ligand 2, or IL-8. The effects were larger in mania phases than in euthymia phases for TNF-a, sIL-2R and IL-1RA. The effect was larger in mania phases than in depression phases for IL-6. In cerebrospinal fluid, moderate quality evidence shows small effects of increased IL-1b and IL-8, and a large effect of increased kynurenic acid.

Moderate quality evidence suggests increased YKL-40, TNF-a, sTNF-R1, IL-6, IL1-Ra, CD40 ligand and CRP are associated with poorer cognitive functioning.

April 2019

Last updated at: 2:17 am, 9th April 2019
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