Treating atherosclerosis as an autoimmune inflammatory disease

Atherosclerosis is a disease characterized by plaque formation in an artery in response to inflammation in the lining (endothelium) of the vessel. It is referred to also as vulnerable plaque because it is subject to rupture followed by the blocking of a smaller downstream artery, the immediate cause of most heart attacks and strokes. A paper recently published in Immunology Letters discusses the treatment of the vascular inflammation of atherosclerosis as an autoimmune inflammatory disorder. The authors state:

"Atherosclerosis is a chronic inflammatory disease, in which multiple types of immune cells are involved. Th1 and Th17 cells play a prominent role in induction and progression of local inflammation in the atherosclerotic plaque."

Note that Th17 cells play a key role in the cascade of factors that produce autoimmune inflammation. Inadequate regulatory T cell (Treg) activity contributes by failing to restrain the autoimmune attack:

"Regulatory T cells (Tregs) can be also found in the plaque but their numbers are decreased and function may be impaired. Tregs are the master modulators of the immune system possessing the immunosuppressive capacity to prevent unfavorable immune responses and maintain tolerance to self-antigens. These cells play the atheroprotective role by inhibiting Th1/Th17-mediated proinflammatory response and down-regulating the antigen-presenting function of dendritic cells (DCs). Tregs mediate the immune response through the cell-to-cell contacts and secretion of anti-inflammatory cytokines IL-10 and TNF-beta."

Improving the function of regulatory T cells is one of the important tactics to ameliorate underlying contributing causes of autoimmune disorders:

"In addition to the natural CD4+CD25+Foxp3+ Tregs presented in the thymus, there are several subtypes of inducible Tregs that can be induced from naïve CD4+ T cells by tolerogenic DCs in the periphery. Thus, stimulation of the immunosuppressive activity of Tregs and increasing numbers of Tregs and immunocompetent DCs has a great clinical potential in prevention and treatment of atherosclerosis and its vascular complications."

In addition to ascertaining adequate 25-OH Vitamin D levels and ensuring that vitamin D receptors (VDR) are working well (both necessary for Treg production), I suggest that clinicians consider low dose cytokine therapy* to promote IL-10 activity. The authors conclude:

"A promising strategy to induce the anti-atherogenic immune response is an oral administration of anti-inflammatory immunomodulators capable to activate the intestine immune tolerance by recruiting mucosal tolerogenic DCs and inducing Tregs. Induced Tregs can then migrate to the inflamed vascular sites and reduce atherogenesis."

* Practitioners are welcome to contact me to discuss low dose cytokine therapy.