Volatile organic compounds: A proinflammatory activator in autoimmune diseases

Abstract

The etiopathogenesis of inflammatory and autoimmune diseases, including pulmonary disease, atherosclerosis, and rheumatoid arthritis, has been linked to human exposure to volatile organic compounds (VOC) present in the environment. Chronic inflammation due to immune breakdown and malfunctioning of the immune system has been projected to play a major role in the initiation and progression of autoimmune disorders. Macrophages, major phagocytes involved in the regulation of chronic inflammation, are a major target of VOC. Excessive and prolonged activation of immune cells (T and B lymphocytes) and overexpression of the master pro-inflammatory constituents [cytokine and tumor necrosis factor-alpha, together with other mediators (interleukin-6, interleukin-1, and interferon-gamma)] have been shown to play a central role in the pathogenesis of autoimmune inflammatory responses. The function and efficiency of the immune system resulting in immunostimulation and immunosuppression are a result of exogenous and endogenous factors. An autoimmune disorder is a by-product of the overproduction of these inflammatory mediators. Additionally, an excess of these toxicants helps in promoting autoimmunity through alterations in DNA methylation in CD4 T cells. The purpose of this review is to shed light on the possible role of VOC exposure in the onset and progression of autoimmune diseases.

Keywords: VOC; autoimmune diseases; immune system and etiopathogenesis; proinflammatory mediators.

Figure 1

Proposed mechanism of volatile organic compound-induced inflammatory response and autoimmune diseases. Black solid arrows represent known pathways, and the black dashed arrows show an assumed mechanism, thus requiring future research.

Figure 2

Common autoimmune diseases associated with VOC exposure.

Figure 3

Immune response is triggered by genetic and environmental factors in the pathogenesis of rheumatoid arthritis (RA). The triggering process causes citrullination of target proteins found throughout the body, which results in the production of autoantibodies (ACPA) against citrullinated neoantigens. Increased levels of citrullinated neoantigens activate MHC class-II-dependent T cells to support B cells in producing more ACPA, which trigger cytokine production by recruiting other immune cells to the synovial joint, resulting in RA.

Figure 4

Immune response triggered by genetic and environmental factors in the pathogenesis of systemic lupus erythematosus. Apoptosis is induced by the triggering agent through cascades of cellular signaling and inflammatory responses. The apoptotic autoantigens released during the process activate antigen-presenting cells (APCs) and neutrophils, promoting thrombosis and tissue damage. Activated APC causes T cells to produce cytokines and B cells to produce other antibodies and complexes, resulting in tissue damage.