Inflammatory Diseases, Deadly Modern Environments / ASD, Depression

quick summation from Torrey Institute for Molecular Studies: 

Inflammatory Disorders (click here for website)

Inflammation is the body’s protective response to injury and infection; it is a complex process involving many cell types, as well as different components of blood.

The inflammatory process works quickly to destroy and eliminate foreign and damaged cells, and to isolate the infected or injured tissues from the rest of the body. Inflammatory disorders arise when inflammation becomes uncontrolled, and causes destruction of healthy tissue. There are dozens of inflammatory disorders. Many occur when the immune system mistakenly triggers inflammation in the absence of infection, such as inflammation of the joints in rheumatoid arthritis. Others result from a response to tissue injury or trauma but affect the entire body.

There are many ways by which normal cells and tissues can be damaged during inflammation. One important mechanism is by assembly of a complex of proteins that forms holes on the surface of a cell, where it causes damage and can potentially kill the cell. This complex is called a Membrane Attack Complex or MAC. Torrey Pines Institute researchers are working to understand how MAC contributes to a number of inflammation-associated disorders, including the complications of diabetes and rheumatoid arthritis. Understanding how MAC assembles will provide insights into the design of drugs to prevent inflammatory damage to cells.

Inflammation is also an important secondary component of many diseases. An example of this is atherosclerosis, or hardening of the arteries, where inflammation can cause more damage to arteries in a failed attempt to heal the artery wall. There is also an important link between obesity and inflammation, because substances that promote inflammation are released from fat cells, as well as from other cells embedded in fat tissue. The Institute’s scientists are leading the way in understanding these new and exciting areas of inflammation research.

The first article below presents the hypothesis that psychological stress and depression may be associated with “inflammatory” diseases.

The second presents the evolutionary “Inflammatory Bias” that has lead to rampant inflammatory disease in modern humans.

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Article 1: Brain Behav Immun. Author manuscript; available in PMC 2014 Jul 1.

 Published in final edited form as: Brain Behav Immun. 2013 Jul; 31: 1–8. Published online 2013 Apr 30. doi:  10.1016/j.bbi.2013.04.009

Malaise, Melancholia and Madness: The Evolutionary Legacy of an Inflammatory Bias

Technical paper, so I’m looking for a credible translation into common language!

Excerpt that may possibly be significant to ASD, Asperger’s and other “social” disorders.  

 5a. Immune Pathways and the Inflammasome

In a paper in this issue, Iwata et al. propose the provocative hypothesis that the recently characterized inflammasome may serve as a critical link between psychological stress and depression, as well as other illnesses related to inflammation (Iwata et al. 2012).

The inflammasome is a protein complex that can detect diverse danger signals including not only pathogen-associated molecules but also molecules associated with cellular damage such as adenosine triphosphate (ATP). Upon activation, the inflammasome can generate an inflammatory response notably through the production of IL-1-beta by activation of a caspase that cleaves the precursor peptide pro-IL-1-beta. Given the capacity of the inflammasome to react to danger signals generated by stimuli other than pathogens, the authors suggest that the inflammasome may be uniquely poised to serve as the molecular mechanism that transduces psychological responses to stress into an inflammatory response in the absence of pathogen challenge.

Thus, the inflammasome may represent an evolutionary adaptation that extends the immune and behavioral response to pathogens and the microbial world to include challenges emanating from predators, people and the social world. Although of significant value in detecting and responding to tissue damage and destruction, by virtue of the inflammasome,

the inflammatory bias may have been given an entrée into the modern world where people, not pathogens or predators represent the primary challenges.

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Article 2:

The role of inflammation in depression: from evolutionary imperative to modern treatment target

Andrew G. Miller and Charles L. Raison

Nature Reviews Immunology Volume:16,Pages:22–34Year published:(2016)DOI:doi:10.1038/nri.2015.5 (click to access article)

Fig. 1 Evolutionary legacy of an inflammatory bias. Early evolutionary pressures derived from human interactions with pathogens, predators and human conspecifics (such as rivals) resulted in an inflammatory bias that included an integrated suite of immunological and behavioural responses that conserved energy for fighting infection and healing wounds, while maintaining vigilance against attack.This inflammatory bias is believed to have been held in check during much of human evolution by exposure to minimally pathogenic, tolerogenic organisms in traditional (that is, rural) environments that engendered immunological responses characterized by the induction of regulatory T (TReg) cells, regulatory B (BReg) cells and immunoregulatory M2 macrophages as well as the production of the anti-inflammatory cytokines interleukin-10 (IL-10) and transforming growth factor-β (TGFβ). In modern times, sanitized urban environments of more developed societies are rife with psychological challenges but generally lacking in the types of infectious challenges that were primary sources of morbidity and mortality across most of human evolution. In the absence of traditional immunological checks and balances, the psychological challenges of the modern world instigate ancestral immunological and behavioural repertoires that represent a decided liability, such as high rates of various inflammation-related disorders including depression.

In proper perspective, modern social environments ARE DEADLY to life; not only to ASD Asperger people, but to ALL HUMANS and to every species that we are driving to extinction – Mass extinction is the likely outcome.

 

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