Systemic inflammation

Rheumatoid arthritis (RA) is a complex systemic inflammatory condition manifesting initially as symmetric swollen and tender joints of the hands and/or feet. Some patients may experience mild articular disease, whereas others may present with aggressive disease and/or extraarticular manifestations. The systemic inflammation of RA leads to joint destruction, disability, and premature death. 

Half of all deaths in RA patients are cardiovascular-related.11 Because a patient with RA experiences inflammation and swelling in his or her joints, it is likely that there is inflammation elsewhere, such as in the blood vessels, termed vasculitis. C-reactive protein (CRP), a nonspecific marker of inflammation, is associated with an increased risk of cardiovascular disease CRP is elevated in patients with RA. Chronic systemic inflammation may contribute to the relationship between RA and cardiovascular disease, but the exact mechanism is still under investigation.11,12... 

Sepsis is a continuum of physiologic stages characterized by infection, systemic inflammation, and hypoperfusion with widespread tissue injury.1 The American College of Chest Physicians and the Society of Critical Care Medicine developed definitions to utilize for sepsis (Table 79—l).2 They provide physiologic parameters categorizing patients as having bacteremia, infection, systemic inflammatory response syndrome (SIRS), sepsis, severe sepsis, septic shock, or multiple-organ-dysfunction syndrome (MODS).2 Standardized definitions have been developed for infections in critically ill patients.3... 

Direct evidence of a neuronal-microglia communication mechanism through the fractalkine system came from in vivo experiments using CX3CR1-deficient mice showing that neuronal-derived fractalkine and its interaction with fractalkine receptor plays a critical role in tonic inhibition of microglial mediated neurotoxicity (66). In three clinically relevant models—CNS response to systemic inflammation, the l-methyl-4 phenyl-1,2,3,6 tetra-hydropyridine (MPTP)... 

Free radicals are supposed to have a significant role in the progression of acute pancreatitis. The involvement of free radicals was firstly demonstrated in many animal models [355,356], Later on, it has been shown that the levels of superoxide and lipid peroxides increased in the blood from patients with acute pancreatitis [357], Rahman et al. [358] found enhanced urinary nitrite excretion in patients with severe acute pacreatitis. It was suggested that this fact is not simply a reflection of systemic inflammation but probably a consequence of the endotoxin-mediated upregulation of inducible NO synthase. 

Headache, tachypnea, dizziness, confusion, and chest pain. The casualty may also experience palpitations, dyspnea on exertion, drowsiness, lethargy, hallucination, agitation, nausea, vomiting, diarrhea, and coma. If metal carbonyls have been released, there may be complaints of irritation of the eyes, mucous membrane, and respiratory system. Inflammation of lung tissue (pneumonitis) caused by metal carbonyls can may be delayed 12-36 hours. They may also cause injury to the liver, kidneys, and lungs as well as degenerative changes in the central nervous system. 

Susceptibility factors increase the risk for kidney disease but do not directly cause kidney damage. Susceptibility factors include advanced age, reduced kidney mass and low birth weight, racial or ethnic minority, family history, low income or education, systemic inflammation, and dyslipidemia. 

La Flamme AC, Ruddenklau K, Backstrom BT Schistosomiasis decreases central nervous system inflammation and alters the progression of experimental autoimmune encephalomyelitis. Infect Immun 2003 71 4996-5004. 

The third type of response to injury, which falls under the general heading of inflammation (suffix itis ), manifests itself in several complex ways. It involves extracellular processes and cells of the immune system. Inflammation is often part of the road to repair from injury, but the inflammatory process can, if extensive, be highly damaging. Inflammation can be acute or chronic in nature. Repair can occur by regeneration of cells, for example by enhanced growth of adjacent cells or it can occur by a process called fibrosis. Some examples of inflammatory responses and repair are brought out in Chapter 4. 

Louis, E., Vermeire, S., Rutgeerts, P., et al. (2002) A positive response to infliximab in Crohn disease association with a higher systemic inflammation before treatment but not with -308 TNF gene polymorphism. Scand. J. Gastroenterol. 37, 818-824. 

DinareUo CA. Therapeutic strategies to reduce lL-1 activity in treating local and systemic inflammation. Curr Opin Pharmacol 2004 4 378-85. 

Gopinath, C. (1996) Pathology of toxic effects on the immune system. Inflammation Research, 45, S74-S78. 

CN202 Kozak, W., D. Soszynski, K. Rudolph, C. A. Conn, and M. J. Kluger. Dietary n-3 fatty acids differentially affect sickness behavior in mice during local and systemic inflammation. Am J Physiol 1997 272(4 Pt. 2) 1298-1307. 

Systemic inflammation Acute respiratory distress syndrome (sustained therapy with moderate dosage accelerates recovery and decreases mortality)... 

Tumor necrosis factor-a A cytokine or messenger protein involved in systemic inflammation and other biological processes. 

In primary cultures of neonatal cerebellar granule neurons, all Ca2+ sensors, calmodulin, protein kinases C (PKC), and the p21(ras)/phosphatidylinositol 3 -kinase (Ptdlns-3K)/Akt pathway, converge towards NF-kB at the levels of nuclear translocation as well as transcription. The duration of NF-kB activation is a critical determinant for sensitivity toward excitotoxic stress and is dependent on the different upstream and downstream signaling associated with various kinases. This is in contrast to studies in non-neuronal cells, which either do not respond to Ca2+ or do not simultaneously activate all three cascades (Lilienbaum and Israel, 2003). Collective evidence suggests that brain inflammatory processes differ from systemic inflammation not only in the involvement of various types of neural cells but also in differences in response to second messengers. 

Systemic inflammation, represented in large part by the production of proinflammatory cytokines, is the response of humans to the assault of the nonself on the organism. 

Jousilahti R et al. Association of markers of systemic inflammation, C reactive protein, serum amyloid A, and fibrinogen, with socioeconomic status. J Epidemiol Community Health 2003 57(9) 730-733. 

Monaco C, Rossi E, Milazzo D, et al. Persistent systemic inflammation in unstable angina is largely related to atherothrombotic burden. J Am Coll Cardiol 2005 45 238-243. 

Kielian, T., and Drew, P. D. (2003). Effects of peroxisome proliferator-activated receptor-gamma agonists on central nervous system inflammation. J. Neurosci. Res. 71, 315-325. 

Treatment of gastrointestinal system inflammations may lead to damage to delicate structures within the system by antibiotics and to physiological bacterial flora selection. 

TNF-a is a cytokine involved in systemic inflammation and is a member of a group of cytokines that stimulate the acute-phase reaction. 

Mayhan WG (1999) VEGF increases permeability of the blood-brain barrier via a nitric oxide synthase/cGMP-dependent pathway. Am J Physiol 276 C1148-C1153 McColl BW, RothweU NJ, AUan SM (2008) Systemic inflammation alters the kinetics of cerebrovascular tight junction disruption after experimental stroke in mice. J Neurosci 28 9451-9462... 

Wong M-L, Bongiorno PB, Rettoii V, McCann SM, lid J (1997) Interleukin (IL) Ip, IL-1 receptor antagonist, lL-10, and lL-13 gene expression in central nervous system and anterior pituitary during systemic inflammation with pathophysiological implications. Proc Natl Acad Sci USA 94 227-232... 

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