Pneumonia-Induced Inflammation, Resolution and Cardiovascular Disease: Causes, Consequences and Clinical Opportunities

Abstract

Pneumonia is inflammation in the lungs, which is usually caused by an infection. The symptoms of pneumonia can vary from mild to life-threatening, where severe illness is often observed in vulnerable populations like children, older adults, and those with preexisting health conditions. Vaccines have greatly reduced the burden of some of the most common causes of pneumonia, and the use of antimicrobials has greatly improved the survival to this infection. However, pneumonia survivors do not return to their preinfection health trajectories but instead experience an accelerated health decline with an increased risk of cardiovascular disease. The mechanisms of this association are not well understood, but a persistent dysregulated inflammatory response post-pneumonia appears to play a central role. It is proposed that the inflammatory response during pneumonia is left unregulated and exacerbates atherosclerotic vascular disease, which ultimately leads to adverse cardiac events such as myocardial infarction. For this reason, there is a need to better understand the inflammatory cross talk between the lungs and the heart during and after pneumonia to develop therapeutics that focus on preventing pneumonia-associated cardiovascular events. This review will provide an overview of the known mechanisms of inflammation triggered during pneumonia and their relevance to the increased cardiovascular risk that follows this infection. We will also discuss opportunities for new clinical approaches leveraging strategies to promote inflammatory resolution pathways as a novel therapeutic target to reduce the risk of cardiac events post-pneumonia.

Inflammatory and endothelial host responses in community-acquired pneumonia: exploring the relationships with HbA1c, admission plasma glucose, and glycaemic gap—a cross-sectional study

“…The immune response to CAP is a complex process of innate and adaptive immunity mediated by pro-inflammatory responses, endothelial activation, and pneumonia resolution mediated by anti-inflammatory responses ( 2 , 26 , 27 ). Preclinical in vitro and in vivo studies have shown that acute hyperglycaemia induces proinflammatory cytokine and chemokine responses and endothelial activation ( 28 – 30 ), while type 2 diabetes is associated with dysregulated immune responses and endothelial dysfunction ( 11 ).…”

Pulmonary toxicity associated with high-dose favipiravir and treatment options: biochemical and histopathological evaluation.

“…This is consistent with the literature reporting that histopathologic damage in lung tissue is associated with oxidant/antioxidant levels 49,50 . Pneumonia is a widely recognized condition characterized by inflammation of the lungs, typically due to an infection 51 . There is currently no information available in the litera-ture suggesting that favipiravir induces interstitial inflammation via oxidative stress in the lungs.…”

Immunizing hearts: exploring the vaccination frontier in heart failure management

“…Similarly, pneumococcal infection induces oxidative stress and triggers inflammatory markers that can lead to thrombogenesis (formation of blood clots), destabilization of atherosclerotic plaques (hardening or narrowing of arteries due to plaque buildup), and endothelial dysfunction. Consequently, pneumococcal infections amplify the likelihood of developing HF 22 .…”