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Interleukin-6 and the Lung
Published in Jason Kelley, Cytokines of the Lung, 2022
Ralph J. Zitnik, Jack A. Elias
In response to infection, trauma, and malignancy, and in association with several immunological disorders, elevations in body temperature, increased vascular permeability, negative nitrogen balance, and alterations in plasma metal ion concentrations occur (Sehgal, 1990). These changes are accompanied by an increase in hepatic amino acid, zinc, and iron uptake and alterations in hepatic production of acute-phase reactant proteins (Baumann and Gauldie, 1990). The acute-phase proteins are involved in various aspects of the organism’s attempt to control and sequester infection and limit the tissue damage that occurs as a result of the primary immune response. An important characteristic of the acute-phase response is that it is elicited by injury or infection at a localized site in the body, implying that soluble factors produced at local sites of injury are able to act at a distance to alter hepatic function.
Evaluation of the Dermal Irritancy of Chemicals
Published in David W. Hobson, Dermal and Ocular Toxicology, 2020
The majority of acute phase proteins is synthesized in hepatocytes, under the influence of circulating mediators released in association with inflammation and necrosis, and, during acute inflammatory processes, the extent of the acute phase response has a quantitative relationship with the degree of inflammation.90 The acute phase response is observed not only in man, but in all mammals, as well as birds, although the major acute phase proteins vary between species. While in the human, CRP and SAA represent the major acute phase proteins, CRP is the major acute phase protein in rabbits, SAA and serum amyloid-P (SAP), which has remarkable structural similarity to CRP, are important in the mouse, and alpha1-acid glycoprotein and alpha2-macroglobulin are predominant in the rat. As immunoassay techniques and instrumentation improve, the measurement of acute phase proteins in blood or local tissue may well serve as the most sensitive and quantitative indicator of inflammation, and become routinely used for this purpose.
Extrahepatic Synthesis of Acute Phase Proteins
Published in Andrzej Mackiewicz, Irving Kushner, Heinz Baumann, Acute Phase Proteins, 2020
Gerhard Schreiber, Angela R. Aldred
Cells in higher animals can only survive and function properly in an environment of appropriate composition (“la fixité du milieu intérieur est la condition de la vie libre”).1 Various regulatory mechanisms ensure that the composition of this environment is kept relatively constant. The achieved state of equilibrium has been called homeostasis.2,3 Proteins are essential components of the fluids filling the extracellular environment. The ultimate function of the acute phase proteins and the purpose of the acute phase response is the maintenance of extracellular homeostasis. The site for this function is extravascular, i.e., in the immediate vicinity of cells or at the barrier structures delineating body compartments.
Current status and prospects of IL-6–targeting therapy
Published in Expert Review of Clinical Pharmacology, 2022
Masashi Narazaki, Tadamitsu Kishimoto
The observation of the congenital loss of the IL-6 receptor is helpful to understand the role of IL-6 in humans. Two patients with homozygous mutations in IL6R gene were reported [88]. The patients lacked an adequate inflammatory response, demonstrated a lack of erythema, and experienced barely elevated fevers even with abscesses. Acute-phase proteins were not elevated despite high elevations in serum IL-6 levels. They suffered from recurrent bacterial infections in the sinuses, lungs, and deep skin, but no significant viral infections were noted. They also suffered from allergic symptoms such as asthma and moderate atopic dermatitis. Serum levels of IgG, IgA, and IgM were mildly reduced, but levels of IgE were high. Infectious episodes were characterized more markedly by eosinophilia than neutrophilia. Immunophenotyping revealed an elevated proportion of CD4 T cells expressing Th2-associated GATA3, an elevated proportion of FOXP3 Treg cells, and a reduced number of class-switched memory B cells. Immunoglobulins included a higher proportion of IgE and IgG4.
What moderates salivary markers of inflammation reactivity to stress? A descriptive report and meta-regression
Published in Stress, 2021
Danica C. Slavish, Yvette Z. Szabo
Inflammation is a broad physiological process that protects against infection and injury, and is an important correlate of stress and health (Ahmed, 2011). Inflammation can be measured by assessing levels of circulating inflammatory biomarkers, such as cytokines or acute phase proteins (Del Giudice & Gangestad, 2018). A growing literature has examined these markers of inflammation in saliva, as its ease of collection offers methodological advantages over more invasive measures like blood. Many salivary markers of inflammation increase in response to acute stress, but there is considerable variability in responses (Szabo et al., 2020; Slavish et al., 2015). Understanding methodological and demographic factors that influence their reactivity to stress may reveal which study designs are most effective for eliciting salivary immune responses to stress, as well as what individuals are most susceptible to stress-related increases in these markers.
TIMP-1 Mediates Inflammatory and Immune Response to IL-6 in Adult Orbital Xanthogranulomatous Disease
Published in Ocular Immunology and Inflammation, 2020
Xia Ding, Yuan Cao, Yue Xing, Shengfang Ge, Ming Lin, Jin Li
The above mentioned results showed that TIMP-1 was upregulated in AOXGD tissues, and previous investigations revealed that TIMP-1 is upregulated in a coordinated early response to IL-6 stimulation.19,20 Furthermore, IL-6, the most important mediator of acute-phase protein synthesis, is required for modulating the dynamics of innate immune cell recruitment during acute inflammation.16,20,21 Thus, we examined the expression of the classical proinflammatory factor IL-6 by immunohistochemistry, and the results showed that the expression of IL-6 was higher in AOXGD tissues than in normal eyelid tissues (Figure 4). These data implied that the increased expression of IL-6 could induce increased secretion of TIMP-1 from M1 macrophages and thereby contribute to the development of AOXGD.