Pro-Inflammatory Cytokines

and the Neuro-developmental/Psychiatric continuum and other chronic diseases

Val's Take/Conjecture

• The Neuro-Developmental/Psychiatric Continuum is starting to look like other illnesses in which INFLAMMATION is a big key.
• The effects of INFLAMMATION IN UTERO may be important for other illnesses, it is certainly important for the Neuro-Developmental/Psychiatric Continuum.
• According to the University of Michigan Medical School, people with bipolar disorder have more reactive cells.
  • Does that mean, more reactive cells that are producing more pro-inflammatory cytokines?
    • I think it probably does mean that.
      

Cytokine Imbalance in Schizophrenia. From Research to Clinic: Potential Implications for Treatment (2021)

• Gene polymorphisms of several cytokines are associated with the development of the schizophrenia syndrome. In patients with schizophrenia, presence of gene polymorphisms of proinflammatory cytokines, such as IL-1β and IL-6, have been linked to high serum levels of these cytokines. 

Inflammation in Bipolar Disorder (2018)

Elevated levels of pro-inflammatory cytokines

• Bipolar disorder (BD) is a severe and persistent mental illness associated with increased rates of several inflammatory medical comorbidities. Replicated evidence has demonstrated a strong association between BD and elevated levels of pro-inflammatory cytokines.

Inflammatory Cytokine: An Attractive Target for Cancer Treatment (2022)

"The pro-inflammatory cytokines are associated with advanced cancer stages, resistance to immunotherapy, and poor prognoses, such as in objective response and disease control rates, and progression-free and overall survival.

"In this review, we selected colorectal, pancreatic, breast, gastric, lung, and prostate cancers, which are well-reported for an association between cancer and inflammatory cytokines."

"The related cytokines and their effects on each cancer’s development and prognosis were summarized.

In addition, the treatment strategies targeting inflammatory cytokines in each carcinoma were also described here. By understanding the biological roles of cancer-related inflammatory cytokines, we may modulate the inflammatory tumor microenvironment for potential cancer treatment.

The causal relationship between 41 inflammatory cytokines and hypothyroidism: bidirectional two-sample Mendelian randomization study (2023)

"The high rate of comorbidity between hypothyroidism and psychiatric disorders deserves special attention, indicating the importance of consistent monitoring and timely identification of psychiatric symptoms to prevent disease exacerbation and facilitate therapeutic management."

Role of pro-inflammatory cytokines released from microglia in neurodegenerative diseases  (2011)

• Microglia are activated in response to a number of different pathological states within the CNS including injury, ischemia, and infection.
• Microglial activation results in their production of pro-inflammatory cytokines such as IL-1, IL-6, and TNF-α
  

Maternal immune activation alters fetal and neonatal microglia phenotype and disrupts neurogenesis in mice

Maternal immune activation (MIA) alters microglial phenotypes in the brain of fetal and neonatal mouse offspring. MIA leads to excessive proliferation and overproduction of neural progenitors in the subventricular zone (SVZ). MIA reduces parvalbumin+ while increases Reelin+ interneurons in the prefrontal cortex.

Maternal immune activation and neuroinflammation in human neurodevelopmental disorders (2021)

Abstract

"Maternal health during pregnancy plays a major role in shaping health and disease risks in the offspring.

"The maternal immune activation hypothesis proposes that inflammatory perturbations in utero can affect fetal neurodevelopment, and evidence from human epidemiological studies supports an association between maternal inflammation during pregnancy and offspring neurodevelopmental disorders (NDDs).

"Diverse maternal inflammatory factors, including obesity, asthma, autoimmune disease, infection and psychosocial stress, are associated with an increased risk of NDDs in the offspring.

"In addition to inflammation, epigenetic factors are increasingly recognized to operate at the gene-environment interface during NDD pathogenesis.

"For example, integrated brain transcriptome and epigenetic analyses of individuals with NDDs demonstrate convergent dysregulated immune pathways.

"In this Review, we focus on the emerging human evidence for an association between maternal immune activation and childhood NDDs, including autism spectrum disorder, attention-deficit/hyperactivity disorder and Tourette syndrome.

"We refer to established pathophysiological concepts in animal models, including immune signalling across the placenta, epigenetic 'priming' of offspring microglia and postnatal immune-brain crosstalk.

"The increasing incidence of NDDs has created an urgent need to mitigate the risk and severity of these conditions through both preventive strategies in pregnancy and novel postnatal therapies targeting disease mechanisms."