It's time to redefine inflammation

Abstract

Inflammation has been defined for many years as the response to tissue injury and infection. We are now forced to reconsider this definition by the avalanche of reports that molecules and cells associated with inflammation are activated or expressed in high concentration in a large variety of states in the absence of tissue injury or infection. Modest increases in concentration of C-reactive protein, a circulating marker of inflammation, have been reported to be associated with an astounding number of conditions and lifestyles felt to be associated with poor health; these conditions represent or reflect minor metabolic stresses. In recent years we have learned that inflammation is triggered by sentinel cells that monitor for tissue stress and malfunction-deviations from optimal homeostasis-and that molecules that participate in the inflammatory process play a role in restoring normal homeostasis. Accordingly, we suggest that inflammation be redefined as the innate immune response to potentially harmful stimuli such as pathogens, injury, and metabolic stress.-Antonelli, M., Kushner, I. It's time to redefine inflammation.

Specific Commensal Bacterium Critically Regulates Gut Microbiota Osteoimmunomodulatory Actions During Normal Postpubertal Skeletal Growth and Maturation

“…Acute‐phase reactants are liver‐derived innate immune factors that are secreted into the circulation . Serum factors were initially classified as acute‐phase reactants based on observations during the acute‐phase of microbial infections, but are now known to be induced during both acute and chronic inflammatory states . Acute‐phase reactants have antimicrobial properties that function in the elimination of pathogenic microbes, but their role in regulating commensal microbes is largely unknown.…”

“…(79)(80)(81)(82)(83) Serum factors were initially classified as acutephase reactants based on observations during the acute-phase of microbial infections, (84,85) but are now known to be induced during both acute and chronic inflammatory states. (85)(86)(87) Acutephase reactants have antimicrobial properties that function in the elimination of pathogenic microbes, but their role in regulating commensal microbes is largely unknown. Acute-phase reactant gene expression analysis in livers included evaluating C-reactive protein (Crp), serum amyloid A 1 (Saa1), hepcidin antimicrobial peptide (Hamp), complement component 3 (C3), and lipocalin-2 (Lcn2).…”

“…Liver-derived acute-phase reactants are secreted into circulation and can have endocrine signaling effects at extrahepatic sites. (82,83,85,87) To discern if acute-phase reactants that were elevated in the livers of MPF versus EF mice were altered in circulation, serum was isolated from whole blood and tested for C3 and LCN2 via ELISA. No differences were detected in C3 levels (Fig.…”

Melatonin as an Anti-Inflammatory Agent Modulating Inflammasome Activation

“…This concept was recently updated due to the avalanche of reports in which molecules and cells associated with inflammation are involved also in the absence of tissue injury or infection. Thus, inflammation may be defined as the innate response to harmful stimuli such pathogens, injury, and metabolic stress, and its ultimate function is to restore the physiological homeostatic state [ 83 ]. However, the exact aetiology leading to the development of inflammation is not known, but a combination of genetic, epigenetic, and environmental factors seems to play an important role [ 84 – 86 ].…”

Impact of Inflammation on Ferritin, Hepcidin and the Management of Iron Deficiency Anemia in Chronic Kidney Disease

“…Inflammation as defined by the innate immune response to stimuli such as pathogens, cellular injury and metabolic stress [ 13 ] is part of the complex biologic response to tissue injury, infection, ischemia and autoimmune diseases. It is characterized by the acute-phase response including elevated inflammation markers such as C-reactive protein (CRP, >0.3 mg/dL) [ 14 ] and pro-inflammatory cytokines which promote CRP synthesis [ 15 ].…”