Interleukin-1beta may act on hepatocytes to boost plasma homocysteine – The increased cardiovascular risk associated with elevated homocysteine may be mediated by this cytokine

• Published in: Medical hypotheses Vol. 102; pp. 78 - 81
• Main Authors: McCarty, Mark F., O'Keefe, James H., DiNicolantonio, James J.
• Format: Journal Article
• Language: English
• Published: United States Elsevier Ltd 01.05.2017
• Subjects: Animals; C-reactive protein; Cardiovascular; Coronary Artery Disease; Coronary Artery Disease - blood; Coronary Artery Disease - immunology; Evidence-Based Medicine; Homocysteine; Homocysteine - blood; Homocysteine - immunology; Humans; Immunologic Factors - immunology; Inflammation Mediators - immunology; Interleukin-1beta; Interleukin-1beta - immunology; Interleukin-6; Internal Medicine; Low Density Lipoprotein; Models, Cardiovascular; Models, Immunological; Peptide Fragments - immunology; Rosuvastatin; CRP; C-reactive protein; Cardiovascular; CAD; Low Density Lipoprotein; Interleukin-1beta; Rosuvastatin; IL-1β; Coronary Artery Disease; IL-6; Interleukin-6; CV; CBS; LDL; Homocysteine; SAM; cardiovascular; interleukin-1beta; S-adenosylmethionine; interleukin-6; cystathionine beta-synthase
• ISSN: 0306-9877; 1532-2777; 1532-2777
• DOI: 10.1016/j.mehy.2017.03.022

The results of multi-center trials of B vitamin supplementation reveal that, whereas moderately elevated homocysteine predicts increased risk for coronary disease, it does not play a mediating role in this regard. This essay proposes that interleukin-1beta can act on hepatocytes to suppress expression of the hepatocyte-specific forms of methionine adenosyltransferase; this in turn can be expected to decrease hepatic activity of cystathionine-β-synthase, leading to an increase in plasma homocysteine. It is further proposed that interleukin-1beta (IL-1β) is a true mediating risk factor for cardiovascular disease, and that elevated homocysteine predicts coronary disease because it can serve as a marker for increased IL-1β activity. Potent statin therapy may decrease IL-1β production by suppressing inflammasome activation – thereby accounting for the marked protection from cardiovascular events observed in the classic JUPITER study, in which the enrolled subjects had low-normal Low Density Lipoprotein cholesterol but elevated C-reactive protein.