Targeting the Inflammation Culprit in Patients with Psoriasis/Psoriatic Arthritis and Associated Cardiovascular Comorbidities. Is the IL-17 Inhibitor the New Kid on the Block?

Abstract

Despite half-century old, but comprehensive national and international guidance, evidence of clinical effectiveness and widespread agreement on management of risk factors along with sophisticated measures for primary and secondary prevention of major cardiovascular events, cardiovascular disease remains the dominant cause of death and disability worldwide. Life style changes at population-level (e.g., lower salt and saturated fat consumption or reduced/banned amount of industrially-produced trans fatty acids in specific products, etc.) or changes at individual level (e.g., targeting modifiable risk factors/life style changes affecting smoking/tobacco use, poor diet, high blood cholesterol, high blood pressure, insufficient physical activity, overweight/obesity) have reduced coronary heart disease mortality to variable extent in different countries (mostly so reported in Finland, Iceland and Sweden) at the beginning of the new century. Overall, however, cardiovascular mortality is estimated to increase in the next coming years until 2030 at a cost exceeding US $1044 billion. Several decades of status quo are also noted in the therapeutic spectrum of cardiovascular disease, mainly consisting of variations to LDL-C lowering agents, antihypertensives, anticoagulants, antiplatelets and fibrinolytics. Most of the therapeutic interventions are "tertiary" in nature (probably some 60%), meaning that treatment is instituted once the individual has developed a pathologic condition; "secondary prevention" may cover some 25%-30% (meant to prevent re-occurrence of the condition or occurrence of complications) while "primary prevention" is left with 10%-15% share (most commonly implying life style changes at individual level and rarely pharmacological intervention). For almost three decades, the so-called inflammatory hypothesis has been promoted as a reasonable pathogenetic theory behind initiation and growth of atherosclerotic plaque (Alexander How to cite this paper: Pater, C.

Adalimumab and methotrexate affect the concentrations of regulatory cytokines (interleukin‐10, transforming growth factor‐β1, and interleukin‐35) in patients with plaque psoriasis

“…Psoriasis and atherosclerosis are chronic inflammatory diseases sharing common immunological features, including dysfunctional regulatory T (Treg) lymphocytes. In psoriasis, T cell differentiation from CD4 + naïve cells is determined by the activity of specific transcription factors and cytokine secretion by dendritic cells, whereas in atherosclerosis, endothelial activation and its consequences drive this process 1‐3 . Treg lymphocytes affect other immune cells via direct cytotoxic activity or by secreting cytokines (ie, interleukin [IL]‐10, IL‐35, and transforming growth factor [TGF]‐β), which subsequently target cell signaling through cell membrane receptors 4‐6 .…”

“…Treg lymphocytes affect other immune cells via direct cytotoxic activity or by secreting cytokines (ie, interleukin [IL]‐10, IL‐35, and transforming growth factor [TGF]‐β), which subsequently target cell signaling through cell membrane receptors 4‐6 . Reduced Treg concentrations contribute to the activation of Th1 and Th17 cells, leading to angiogenesis, keratinocyte activation, proliferation, and growth (Th1) in psoriasis as well as atherosclerotic plaque instability and rupture (Th17) 1‐3 . Proinflammatory mediators, such as tumor necrosis factor alpha (TNF‐α), exert effects that contribute to the development of atherosclerosis.…”