Saturday, 27 April 2019

Phytochemical 3,3'-Diindolylmethane, a Natural Prevention and Treatment of Delayed-Type Hypersensitivity

By Kyle J. Norton

Delayed-type hypersensitivity is also known as type 4 hypersensitivity because the reaction takes several days to develop, including contact dermatitis.

Believe it or not, type IV hypersensitivity mediated by antigen-specific effector T cells is associated with the infection induced by slow-growing intracellular organisms, such as M. tuberculosis (tuberculosis), M. leprae (leprosy) and H. capsulatum.

Some researchers suggested that the delayed hypersensitivity is dependent on the presence of a significant number of primed, antigen-specific T cells response which typically reaches its peak 24 to 48 hours after exposure to antigen.

Type IV hypersensitivity diseases although are common, but ranges second to type 1 hypersensitivity.

Many diseases are found to associate with delayed-type hypersensitivity include leprosy, tuberculosis, schistosomiasis, sarcoidosis and Crohn's disease.

Leprosy is divided clinically into three essential types: tuberculoid, borderline, and lepromatous. 

Schistosomiasis caused by schistosomes, once the body is sensitized by a granulomatous reaction developed in the parasitized tissue mediated by Th2 lymphocytes.

Tuberculosis in the lungs caused by a granulomatous reaction that leads to cavitation and the spread of bacteria

Sarcoidosis is a chronic and idiopathic disease caused by the activated macrophage and granuloma accumulation in many tissues along with fibrosis.

Crohn's disease is a granulomatous disease that is not caused by a microorganism. 

3,3'-Diindolylmethane or DIM are phytochemicals derived from the digestion of indole-3-carbinol, belonging to the group of Indoles, found abundantly in broccoli, Brussels sprouts, cabbage, and kale, etc.

On finding a potential ingredients for the prevention and treatment of the delayed-type hypersensitivity, researchers tested the ability of dietary AhR ligands (indole-3-carbinol [I3C] and 3,3'-diindolylmethane [DIM]) and an endogenous AhR ligand, 6-formylindolo(3,2-b)carbazole (FICZ), on the differentiation and functions of Tregs and Th17 cells.

Administration of indoles (I3C or DIM) in tested mice attenuated delayed-type hypersensitivity (DTH) response to methylated BSA, an antigen-specific inflammation in targeted organs and generation of Th17 cells which play a critical role in the induction of the tissue inflammation and tissue destruction while promoting Tregs in the suppression of immune response.

Interestingly, the indoles inhibited the delayed-type hypersensitivity by causing the reciprocal induction of Tregs and Th17 cells only in wild-type (AhR(+/+)) but not in AhR knockout (AhR(-/-)) mice.

Additional analysis of the indoles anti-delayed-type hypersensitivity activity, researchers found that the efficacy of the indoles was associated with the promotion of protein (FoxP3) involved in immune system responses of the Tregs while decreasing the protein associated with pro-inflammatory expression.

In order to reveal more anti-inflammation about indole-3-carbinol (I3C) and diindolylmethane (DIM), researchers investigated the compounds in the exhibition of the characteristics of aryl hydrocarbon receptor (AhR) ligands, that was found to regulate the T cell differentiation.

In a murine model of multiple sclerosis (MS), retreatment with I3C or DIM completely prevented the clinical symptoms and cellular infiltration into the CNS through induction of inflammation.

Particularly, post-treatment of EAE with I3C or DIM proved highly effective in curtailing the overall severity of the disease.

Similar to that of aforementioned protection against delayed-type hypersensitivity, I3C or DIM promoted the generation of T-regs, while inhibited the induction of MOG-specific Th17 cells.

In other words, I3C or DIM inhibited delayed type hypersensitivity through the promotion of T-regs and suppression of Th17 cells in vivo and in vitro were found to be AhR-dependent.

Taken altogether, 3,3'-Diindolylmethane derived from the digestion of indole-3-carbinol may be considered a supplement for the prevention and treatment of delayed type hypersensitivity, pending to the confirmation of the larger sample size and multicenter human study.

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Author Biography
Kyle J. Norton (Scholar, Master of Nutrition, All right reserved)

Health article writer and researcher; Over 10.000 articles and research papers have been written and published online, including worldwide health, ezine articles, article base, health blogs, self-growth, best before it's news, the karate GB daily, etc.,.
Named TOP 50 MEDICAL ESSAYS FOR ARTISTS & AUTHORS TO READ by Named 50 of the best health Tweeters Canada - Huffington Post
Nominated for shorty award over last 4 years
Some articles have been used as references in medical research, such as international journal Pharma and Bioscience, ISSN 0975-6299.

(1) Dietary Indoles Suppress Delayed-Type Hypersensitivity by Inducing a Switch from Proinflammatory Th17 Cells to Anti-Inflammatory Regulatory T Cells through Regulation of MicroRNA by Singh NP1, Singh UP1, Rouse M1, Zhang J2, Chatterjee S3, Nagarkatti PS1, Nagarkatti M. (PubMed)
(2) Indoles mitigate the development of experimental autoimmune encephalomyelitis by induction of reciprocal differentiation of regulatory T cells and Th17 cells by Rouse M1, Singh NP, Nagarkatti PS, Nagarkatti M. (PubMed)
(3) Delayed Hypersensitivity Reactions by Angel A. Justiz Vaillant; Kamleshun Ramphul.(NCBI)

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