Triggers, Timescales, and Treatments for Cytokine-Mediated Tissue Damage

Abstract

Inflammation, an essential cytokine-mediated process for generating a neutralising immune response against pathogens, is generally protective. However, aberrant or excessive production of proinflammatory cytokines is associated with uncontrolled local and systemic inflammation, resulting in cell death and often irreversible tissue damage. Uncontrolled inflammation can manifest over timescales spanning hours to years and is primarily dependent on the triggering event. Rapid and potentially lethal increases in cytokine production, or ‘cytokine storm’, develops in hours to days, and is associated with cancer cell-based immunotherapies, such as chimeric antigen receptor T-cell therapy. On the other hand, some bacterial and viral infections with high microbial replication or highly potent antigens elicit immune responses that result in supraphysiological systemic cytokine concentrations, which manifest over days to weeks. Immune dysregulation in autoimmune diseases can lead to chronic cytokine-mediated tissue damage spanning months to years, which often occurs episodically. Upregulation of IL-1, IL-6, IFN-γ, TNF, and granulocyte macrophage colony-stimulating factor frequently coincides with cytokine storm, sepsis, and autoimmune disease. Inhibition of proinflammatory molecules via antagonist monoclonal antibodies has improved clinical outcomes, but the complexity of the underlying immune dysregulation results in high variability. Rather than a ‘one size fits all’ treatment approach, an identification of disease endotypes may permit the development of effective therapeutic strategies that address the contributors of disease progression. Here, the authors present a literature review of the cytokine-associated aetiology of acute and chronic cytokine-mediated tissue damage, describe successes and challenges in developing clinical treatments, and highlight advancements in preclinical therapeutic strategies for mitigating pathological cytokine production.

Extracts of Waste from Poplar Wood Processing Alleviate Experimental Dextran Sulfate-Induced Colitis by Ameliorating Oxidative Stress, Inhibiting the Th1/Th17 Response and Inducing Apoptosis in Inflammatory Lymphocytes

“…Aberrant or excessive production of proinflammatory cytokines is associated with uncontrolled local and systemic inflammation, leading to cell death and often irreversible tissue damage. The inhibition of excessive effector functions is a key factor in the treatment of inflammatory diseases [ 39 , 40 ]. In IBD animals, the infiltration of inflammatory cells damages colonic tissues and is detrimental to the lives of these animals.…”

Nutraceuticals and Herbs in Reducing the Risk and Improving the Treatment of COVID-19 by Targeting SARS-CoV-2

“…Cinchona plant from Andean Mountain forests provides substantial benefits since a particular portion of the trees produce bioactive compounds that may help cure fever, and Jesuit missionaries were the first to notice this beneficial influence, which spread across the world [ 104 ]. Quinine is a plant-derived medicine currently under investigation for COVID-19 treatment that was discovered as the principal bioactive compound in Cinchona officinalis , a south American antimalarial medicinal plant [ 105 ].…”

Cellular heterogeneity in TNF/TNFR1 signalling: live cell imaging of cell fate decisions in single cells

“…Conducting experiments in live mice enables the continuous tracking of physiological changes over an extended period within the same research subject. This is particularly useful for studying cellular responses to TNF, as inflammation and cell death can manifest over a range of timescales, spanning from hours to years, depending on whether the response is acute or chronic [ 218 , 219 ]. This approach can also be utilised to conduct experiments such as lineage tracing, allowing for the constant monitoring of cell-fate decisions over time [ 220 , 221 ].…”