The immune system is the body’s first line of defence. It uses proteins called cytokines that are secreted by immune cells to allow cell-to-cell communication. Cytokines include interleukins (IL), interferons (IFN), tumor necrosis factors (TNF), transforming growth factors (TGF), and chemokines. These have influence over many cell types, including T helper lymphocytes (Th cells, or white blood cells). Cytokines act to regulate immunological and inflammatory responses to pathogens. They function as intermediaries between the immune system and the central nervous system. 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. Alterations to the immune system have been found in bipolar disorder and schizophrenia, and it has also been investigated in people with PTSD.

What is the evidence for changes in the immune system in people with PTSD?

Moderate to high quality evidence found large increases in IFN-γ, IL-2, IL-1β, and IL-6, and medium-sized increases in TNF-α, WBC, and CRP in people with PTSD compared to controls. There were no differences in IL-4, IL-8, IL-10, lymphocyte, B lymphocyte, CD3+ T lymphocyte, CD4+ T lymphocyte, CD8+ T lymphocyte, or NK cell. The effect sizes became non-significant in medicated patients for IL-1β, IL-2, and IL-6. The effect for CD8+ T lymphocyte became significant when using only trauma-exposed controls (reduced levels in patients). When using only non-trauma-exposed controls, the effect for IL-1β became non-significant, while the effect for IL-10 became significant (increased levels in patients). In patients without comorbid major depression, the effect sizes for IL-8 and CD4+ T lymphocyte became significant (increased levels in patients).

August 2021

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Inflammation is caused by the immune system’s response to pathogens or tissue damage. The immune system is the body’s first line of defence and predominantly uses proteins called cytokines that are secreted by immune cells and act to allow cell-to-cell communication. Cytokines include interleukins (IL), interferons (IFN), tumor necrosis factors (TNF), transforming growth factors (TGF), adipokines, and chemokines. C-reactive protein (CRP) is released by the body during inflammation, with increased CRP suggestive of infection and chronic inflammatory conditions such as cardiovascular disease, diabetes, and metabolic dysfunction.

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

Moderate to high quality evidence found medium to large increases in CRP levels in people with bipolar disorder during a manic phase, and medium-sized increases during a depressive phase, when compared to controls. These effects were increased slightly in studies that matched controls for age and body mass index (in depression only), in studies of drug-free patients (in depression only) and in studies using serum rather than plasma measures (in mania only). These effects were not related to symptom severity but were decreased slightly after resolution of the index mood episode.

Moderate quality evidence found IL-8, monocyte-chemoattractant protein-1 (MCP-1), eotaxin-1, and interferon-γ-induced protein 10 (IP-10) were elevated in people with bipolar disorder compared to controls. The elevated levels of IL-8 and MCP-1 appeared only during the depressive phase, while the elevated levels of IP-10 were present only during euthymia. The analysis of eotaxin-1 levels was mainly based on studies of euthymic patients. Small to medium-sized increases were also found in IL-4, IL-6, IL-10. sIL-2R, sIL-6R, TNF-a and sTNFR1 in serum or plasma of people with bipolar disorder. No differences were found in IL-2, IFN-y, C-C motif ligand 2, or IL-1β in serum or plasma. However, small increases were found in IL-1β in cerebrospinal fluid of patients. In separate assessment of acutely ill patients, there were medium to large increases in blood IL-1RA, sIL-2R, IL-6, and TNF-α, with no increases in sIL-6R or IL-10. In chronic patients during euthymia, there were small to medium-sized increases in sIL-2R, sIL-6R, IL-4, sTNF-R1, IL-1β, IL-6, and IL-10, with no increases in IL-2, TNF-α, or IFN-γ.

Moderate to high quality evidence found medium-sized increases in neutrophil/lymphocyte ratio (NLR) and platelet/lymphocyte ratio (PLR) levels in people with bipolar disorder, particularly during a manic phase. Increasing age and male gender were associated with larger effect sizes for NLR but not for PLR. There were small to medium-sized reductions in tryptophan, kynurenine, xanthurenic acid, and kynurenic acid. However, increased kynurenic acid was found in cerebrospinal fluid. The kynurenic acid to kynurenine ratio and the kynurenic acid to quinolinic acid ratio were reduced in bipolar disorder. People in a manic episode had the greatest reductions in tryptophan, while kynurenic acid levels were more reduced in a depressive phase. There were similar reductions in kynurenine in depression and mania phases. Finally, adiponectin levels were significantly higher in bipolar patients during euthymia but may be lower than controls during depression.

December 2021

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