C-reactive protein (CRP) is the best-known acute phase protein. In humans, almost every type of inflammation is accompanied by an increase of CRP concentration. Until recently, the only known physiological function of CRP was the marking of cells to initiate their phagocytosis. This triggers the classical complement pathway up to C4, which helps to eliminate pathogens and dead cells. However, vital cells with reduced energy supply are also marked, which is useful in the case of a classical external wound because an important substrate for pathogens is disposed of, but is counterproductive at internal wounds (e.g., heart attack or stroke). This mechanism negatively affects clinical outcomes since it is established that CRP levels correlate with the prognosis of these indications. Here, we summarize what we can learn from a clinical study in which CRP was adsorbed from the bloodstream by CRP-apheresis. Recently, it was shown that CRP can have a direct effect on blood pressure in rabbits. This is interesting in regard to patients with high inflammation, as they often become tachycardic and need catecholamines. These two physiological effects of CRP apparently also occur in COVID-19. Parts of the lung become ischemic due to intra-alveolar edema and hemorrhage and in parallel CRP increases dramatically, hence it is assumed that CRP is also involved in this ischemic condition. It is meanwhile considered that most of the damage in COVID-19 is caused by the immune system. The high amounts of CRP could have an additional influence on blood pressure in severe COVID-19.

C reactive protein (CRP) levels directly correlate with the disease activity of many inflammatory diseases, e.g. sepsis, infection, and various autoimmunopathies such as rheumatoid arthritis (RA) . In contrast, insufficient CRP levels are implicated in the development of systemic lupus erythematosus (SLE) . This article reports on the level-depended effects of CRP in various diseases. In detail we show that increased and decreased levels of CRP, as demonstrated in patients with RA and SLE, respectively can contribute to disease progression.

Systemic lupus erythematosus (SLE) is a chronic inflammatory disease characterized by the production of autoantibodies, formation of immune complexes (IC), and activation of complement that ultimately fuel acute and/or chronic inflammation. Accumulation in blood and tissues of post-apoptotic remnants is considered of etiological and pathological importance for patients with SLE. Besides receptors directly recognizing apoptotic cells, soluble opsonins of the innate immune system bind apoptotic material dependent on the stage of apoptosis. We describe the binding to the surface of secondary necrotic cells (SNEC) of the serum opsonin CRP and further opsonins. We show that anti-dsDNA and anti-CRP autoantibodies bind and sensitize SNEC. Autoantibody-sensitized SNEC were cleared by macrophages in vitro and induced a pro-inflammatory cytokine response. In conclusion, anti-CRP, CRP, and SNEC form a ternary pyrogen endowed with strong pro-inflammatory capabilities which is able to maintain and perpetuate chronic inflammation.

C-reactive protein (CRP), the prototype human acute phase protein, may be causally involved in various human diseases. As CRP has appeared much earlier in evolution than antibodies and nonetheless partly utilizes the same biological structures, it is likely that CRP has been the first antibody-like molecule in the evolution of the immune system. Like antibodies, CRP may cause autoimmune reactions in a variety of human pathologies. Consequently, therapeutic targeting of CRP may be of utmost interest in human medicine. Over the past two decades, however, pharmacological targeting of CRP has turned out to be extremely difficult. Currently, the easiest, most effective and clinically safest method to target CRP in humans may be the specific extracorporeal removal of CRP by selective apheresis. The latter has recently shown promising therapeutic effects, especially in acute myocardial infarction and COVID-19 pneumonia. This review summarizes the pros and cons of applying this novel technology to patients suffering from various diseases, with a focus on its use in cardiovascular medicine.