Introduction: Interleukin-37 (another name: IL-1F7) is a member of the Interleukin-1 family that exists in a variety of species but not all species have been thoroughly studied yet. IL-1 binds to the IL-18Rα chain and uses TIR8 as the second chain receptor. Its anti-inflammatory activity depends on ASC and NLRP3. Following this article, we will review the effects of IL-37 in inflammation and cardiovascular disease.
IL-37 and Inflammation)
IL-37 is classified as an anti-inflammatory cytokine that reduces the production of TNF-α, IL-1α, IL-6, and IL-8. Decreased expression of IL-37 is an important event in the pathogenesis of many diseases, especially those associated with severe inflammation. IL-37 accumulates significantly in atherosclerotic plaques. Also, the levels of IL-37 expression are increased in the plasma of patients with heart failure and acute coronary syndrome. However, the anti-inflammatory effects of IL-37 can be reduced by the effects of compounds such as TIR-8, and therefore, IL-37 inhibitors may be potential therapeutic agents for inflammatory diseases. IL-37 stimulates and regulates different cells during inflammation. More precisely, in inflammatory conditions, monocytes and dendritic cells are the main producers of IL-37, but in normal physiological conditions, just dendritic cells release IL-37.
The therapeutic effects of interleukin in cardiovascular disease)
The inflammatory response is required for the formation of coronary atherosclerosis plaques. The first stage of the inflammatory response involves activation of DAMPs with stimulation of the TLR pathway. Activation of DAMPs consistently stimulates expression of chemokines to revitalize inflammatory cells and accelerates adhesion of molecules to plaque formation. Vascular Smooth Muscle Cells (VSMC), endothelial cells, T lymphocytes, and macrophages secrete IL-37 in atherosclerotic plaques. Research has shown that interleukin significantly alters the expression of inflammatory cytokines to reduce atherosclerotic plaque formation. Following IL-37 treatment, inflammation was suppressed.
IL-37 in Acute Coronary Syndrome )
ACS is a type of acute cardiovascular disease that includes unstable angina and acute myocardial infarction associated with a rupture that usually accompanied by inflammation. Various studies have shown a positive association between IL-6 and TNF-α levels with the severity of the coronary syndrome and mortality. Notably, IL-37 levels are also significantly elevated in patients with ACS without apparent anti-inflammatory effects.
Cytokines in Heart Failure)
Many reports indicate that the levels of TNF-α, IL-1, IL-6, and IL-18 are increased in patients with heart failure and their increase is directly related to the severity of the failure. Inflammatory cytokines modulate myocardial function by stimulating fibroblasts, ultimately reducing cardiomyocyte contractile function. Inflammatory cytokines (TNF-α and IL-6) are elevated in the acute stages of myocardial infarction, which can lead to hypertrophy. The response of cytokines is completely under the control of the immune system. The levels of inflammatory cytokines in heart failure increase, but they are initially low, so they require sensitive tests and high costs for diagnosis. TNF-α plays an important role in causing heart failure. Thalidomide is known as anti-TNF-α (immunotherapy drug group), used in patients with heart failure and has been shown to reduce mortality. TNF-α levels increased during the analysis but its mechanism of action is still unclear. It has also been shown that chemokines by transferring leukocytes to the inflamed area can lead to a more severe inflammatory response, resulting in impaired cardiomyocyte function and ultimately ventricular deformity.
Methods: In the first study, hospitalized patients with high levels of IL-37 were evaluated. In the second study, the role of T cell-derived interleukin was investigated.
Results: In the first study, the frequency of hospitalization and mortality from heart failure decreased. A second study showed that T-cell-derived interleukin may be regulated automatically and make slow the progression of heart failure through T cells.
Conclusion: Research over the past years on cytokines and the interleukin family has been remarkable, and there is evidence that its members play a role in cardiovascular disease. various studies have shown that most members of this family have exacerbated function in atherosclerosis, myocardial infarction, or stroke. Various clinical trials are currently underway, and their positive results may be conceptual for the involvement of the immune system, especially cytokines, in cardiovascular disease. However, studies indicate the critical role and potential therapeutic potential of the IL-1 family in cardiovascular disease.