{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,12]],"date-time":"2026-10-12T23:38:05Z","timestamp":1791848285662,"version":"4.3.4"},"reference-count":122,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2021,1,29]],"date-time":"2021-01-29T00:00:00Z","timestamp":1611878400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Immunol."],"abstract":"<jats:p>In the blood of healthy individuals C-reactive protein (CRP) is typically quite scarce, whereas its blood concentration can rise robustly and rapidly in response to tissue damage and inflammation associated with trauma and infectious and non-infectious diseases. Consequently, CRP plasma or serum levels are routinely monitored in inpatients to gauge the severity of their initial illness and injury and their subsequent response to therapy and return to health. Its clinical utility as a faithful barometer of inflammation notwithstanding, it is often wrongly concluded that the biological actions of CRP (whatever they may be) are manifested only when blood CRP is elevated. In fact over the last decades, studies done in humans and animals (e.g. human CRP transgenic and CRP knockout mice) have shown that CRP is an important mediator of biological activities even in the absence of significant blood elevation, i.e. even at baseline levels. In this review we briefly recap the history of CRP, including a description of its discovery, early clinical use, and biosynthesis at baseline and during the acute phase response. Next we overview evidence that we and others have generated using animal models of arthritis, neointimal hyperplasia, and acute kidney injury that baseline CRP exerts important biological effects. In closing we discuss the possibility that therapeutic lowering of baseline CRP might be a useful way to treat certain diseases, including cancer.<\/jats:p>","DOI":"10.3389\/fimmu.2020.619564","type":"journal-article","created":{"date-parts":[[2021,1,29]],"date-time":"2021-01-29T05:04:26Z","timestamp":1611896666000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":38,"title":["Therapeutic Lowering of C-Reactive Protein"],"prefix":"10.3389","volume":"11","author":[{"given":"Rachel V.","family":"Jimenez","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alexander J.","family":"Szalai","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2021,1,29]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","DOI":"10.1016\/S0161-5890(01)00042-6","article-title":"Human C-reactive protein: expression, structure, and function","volume":"38","author":"Volanakis","year":"2001","journal-title":"Mol Immunol"},{"key":"B2","doi-asserted-by":"publisher","DOI":"10.1016\/s1537-1891(02)00294-x","article-title":"The biological functions of C-reactive protein","volume":"39","author":"Szalai","year":"2002","journal-title":"Vascul Pharmacol"},{"key":"B3","doi-asserted-by":"publisher","DOI":"10.1385\/IR:26:1-3:279","article-title":"Varied biologic functions of C-reactive protein: lessons learned from transgenic mice","volume":"26","author":"Szalai","year":"2002","journal-title":"Immunol Res"},{"key":"B4","doi-asserted-by":"publisher","DOI":"10.1016\/j.amjmed.2005.06.057","article-title":"What does minor elevation of C-reactive protein signify","volume":"166","author":"Kushner","year":"2006","journal-title":"Am J Med"},{"key":"B5","doi-asserted-by":"publisher","DOI":"10.1007\/s11883-006-0040-x","article-title":"C-reactive protein and cardiovascular disease: weighing the evidence","volume":"8","author":"Lowe","year":"2006","journal-title":"Curr Atheroscler Rep"},{"key":"B6","doi-asserted-by":"publisher","DOI":"10.1016\/j.jacc.2007.06.012","article-title":"C-reactive protein gene polymorphisms, C-reactive protein blood levels, and cardiovascular disease risk","volume":"50","author":"Hage","year":"2007","journal-title":"J Am Coll Cardiol"},{"key":"B7","doi-asserted-by":"publisher","first-page":"295","DOI":"10.1111\/j.1365-2796.2008.02015.x","article-title":"C-reactive protein and coronary heart disease: a critical review","volume":"264","author":"Casas","year":"2008","journal-title":"J Intern Med"},{"key":"B8","doi-asserted-by":"publisher","DOI":"10.3109\/10408363.2011.599831","article-title":"Elevated C-reactive protein in the diagnosis, prognosis, and cause of cancer","volume":"48","author":"Allin","year":"2011","journal-title":"Crit Rev Clin Lab Sci"},{"key":"B9","doi-asserted-by":"publisher","DOI":"10.1155\/2014\/319215","article-title":"Recognition functions of pentameric C-reactive protein in cardiovascular disease","volume":"2014","author":"Agrawal","year":"2014","journal-title":"Mediators Inflammation"},{"key":"B10","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2018.02607","article-title":"Pentraxins and Fc Receptor-Mediated Immune Responses","volume":"9","author":"Lu","year":"2018","journal-title":"Front Immunol"},{"key":"B11","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2018.02382","article-title":"The Pentraxins 1975-2018: Serendipity, Diagnostics and Drugs","volume":"9","author":"Pepys","year":"2018","journal-title":"Front Immunol"},{"key":"B12","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2019.00943","article-title":"Evolution of C-Reactive Protein","volume":"10","author":"Pathak","year":"2019","journal-title":"Front Immunol"},{"key":"B13","doi-asserted-by":"publisher","DOI":"10.1084\/jem.52.4.561","article-title":"Serological Reactions in Pneumonia with a Non-Protein Somatic Fraction of Pneumococcus","volume":"52","author":"Tillett","year":"1930","journal-title":"J Exp Med"},{"key":"B14","doi-asserted-by":"publisher","DOI":"10.1084\/jem.73.2.173","article-title":"The occurrence during acute infections of a protein not normally present in the blood: I. 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