Cytokines, sepsis and immunomodulation

Abstract

Tissue injury and infection produce significant alterations in host metabolic and immune homeostasis. It is increasingly clear that many of these changes result from a complex cascade of mononuclear phagocyte-derived endogenous mediators. Among the more important is a group of host proteins called cytokines, which play an integral role in mediating the host response to tissue injury and infection. Of these proteins, tumour necrosis factor (TNF) and interleukin (IL) types 1 and 6 have received much attention for their pathophysiological roles in infection and trauma. Evidence is reviewed for the involvement of these cytokines in the characteristic alterations in the metabolic and immune responses to such injury. These endogenous mediators initiate an integrated fuel substrate and hormonal adjustment to trauma and sepsis, and help to provide optimal metabolic homeostasis for systemic host defences. Widespread tissue injury, especially when associated with fulminant sepsis, may, however, precipitate massive release of TNF, IL-1 and IL-6, triggering a series of reactions involving multiple organs, and culminating in the 'sepsis syndrome'. New therapies designed to downregulate this aberrant response, either by neutralizing endotoxin directly or by blocking the release or actions of these cytokines, are reviewed. Although these treatments hold much promise for the future management of severely traumatized and infected patients, careful evaluation of both the benefits and complications of therapy is needed before widespread clinical use can be recommended.

Anti-inflammatory Triterpenes from Euonymus alatus Leaves and Twigs on Lipopolysaccharide-activated RAW264.7 Macrophage Cells

“…Among the compounds isolated, abruslactone A (4) and demethylregelin (9) showed the potent inhibitory activities on NO production and iNOS expression in LPS-stimulated RAW264.7 cells. Though further investigations are required to clarify the detailed anti-inflammatory actions of bioactive compounds from E. alatus, the triterpenes isolated herein are thought contribute to anti-inflammatory effects of E. alatus and might possess beneficial therapeutic potential against various inflammation-related diseases.…”

“…6 An effective immune cells, macrophages play pivotal roles in innate and adaptive immune response to pathogens such as phagocystosis, cytokines, bacteria, bacterial products and particulates including lipopolysaccharide (LPS). [7][8][9] Upon activation, various growth factors, cytokines and lipid mediators that promote inflammatory process are released. Hence, macrophages are recognized as target cells of a variety of immunosuppressants and anti-inflammatory drugs, leading to acquired immunity.…”

Local and Systemic Up-regulation of TNFα, IL-1β and IL-6 in Mice Intratracheally Inoculated with Porphyromonas gingivalis

“…Although IL-6 is considered to enter the blood stream immediately after the stimulation of cells with LPS (Wong and Clark 1988;Molloy et al 1993) or live bacteria (Karzai et al 2003), the peak of IL-6 in serum occurred as late as 72 and 168 h after inoculation. IL-6 is supposed to have inhibitory effects on TnF- levels; local application of IL-6 to rats inoculated concurrently with LPS has been reported to inhibit TnF- production (Ulich et al 1991).…”

“…This cytokine acts by binding to specific receptor, leading, together with TnF- and IL-1β, to synthesis and release of acute phase proteins from the liver (Molloy et al 1993;Ebersole et al 2002). Therefore, periodontal disease, which is a chronic infection with periodontopathogenic bacteria (i.e.…”

An anti-human recombinant tumor necrosis factor alpha (TNF?) monoclonal antibody recognizes an epitope in feline TNF?

“…The use of anti-LPS mAb may prevent the septic shock or in vivo animal correlates, such as the Shwartzman reaction [1]. Similarly, anti-TNFα mAb may block the biological activity of the cytokine, preventing the manifestation of the shock syndrome [2,17].…”