Arterial Hypertension and Interleukins: Potential Therapeutic Target or Future Diagnostic Marker?

Abstract

Hypertension as a multifactorial pathology is one of the most important cardiovascular risk factors, affecting up to 30-40% of the general population. Complex immune responses are involved in the inflammatory mechanism of hypertension, with evidence pointing to increased inflammatory mediators even in prehypertensive patients. Increased vascular permeability, thrombogenesis, and fibrosis, effects that are associated with sustained hypertension, could be attributed to chronic inflammation. Chronic inflammation triggers endothelial dysfunction via increased production of ROS through proinflammatory cytokines. Increased serum level of proinflammatory cytokines such as IL-1β, IL-6, IL-8, IL-17, IL-23, TGFβ, and TNFα in hypertensive patients has been associated with either increased blood pressure values and/or end-organ damage. Moreover, some cytokines (i.e., IL-6) seem to determine a hypertensive response to angiotensin II, regardless of blood pressure values. Understanding hypertension as an inflammatory-based pathology gives way to new therapeutic targets. As such, conventional cardiovascular drugs (statins, calcium channels blockers, and ACEIs/ARBs) have shown additional anti-inflammatory effects that could be linked to their blood pressure lowering properties. Moreover, anti-inflammatory drugs (mycophenolate mofetil) have been shown to decrease blood pressure in hypertensive patients or prevent its development in normotensive individuals. Further research is needed to evaluate whether drugs targeting hypertensive-linked proinflammatory cytokines, such as monoclonal antibodies, could become a new therapeutic option in treating arterial hypertension.

Changes of Serum Inflammatory Molecules and Their Relationships with Visual Function in Retinitis Pigmentosa

“… 23 , 24 Increased IL-8 has been shown to be associated with obesity, hypertension, DM, dyslipidemia, and autoimmune diseases. 25 – 28 On the other hand, drugs, such as statins, have been reported to lower serum IL-8. 29 Therefore, we excluded the subjects with these systemic conditions.…”

Immunity and Hypertension

“…107 Multiple other cytokines are associated with hypertension and inflammation, including IL-8, IL-12, IL-15 and IL-18, but more recently IL-22 has shown a stronger link. 108 The CC genotype of IL-22 gene polymorphism is an independent risk factor for hypertension in patients with CAD, while the GG genotype has a protective effect. 109 In mice, treatment with recombinant IL-22 increases blood pressure, whereas anti-IL-22 neutralizing monoclonal antibody decreases blood pressure, inflammatory responses and endothelial dysfunction.…”

“…In contrast, a recent study in a combined model of DOCA salt‐ and Ang II–induced hypertension demonstrates that combined IL‐17/IL‐23 deficiency does not suppress the blood pressure response, illustrating the complex role of the immune system within diverse models of hypertension 107 . Multiple other cytokines are associated with hypertension and inflammation, including IL‐8, IL‐12, IL‐15 and IL‐18, but more recently IL‐22 has shown a stronger link 108 . The CC genotype of IL‐22 gene polymorphism is an independent risk factor for hypertension in patients with CAD, while the GG genotype has a protective effect 109 .…”

Assessment of interleukins 1 and 6 in hypertensive subjects

“…They form a major part of the inflammatory response of the body against infection. Interleukin 6 (IL-6) is a pleiotropic cytokine with a broad range of biologic activities in control of immunological process, production of blood cells, inflammation, and formation of cancerous cells (Tanase et al, 2019). IL-1 also induces its own production and processing which is key in the pathogenesis of many auto inflammatory diseases (Dinarello, 2012;Doria et al, 2012).…”