Speciality
Spotlight

   




   

Surgery


   

 





Immunomodulatory
Therapies of Sepsis

         

  • S.J. Parkar P.E. Watkins

    Immunomodulatory Therapies of Sepsis and SIRS

    Recent Advances in Surgery-23, Year-2000

         

    Inflammation is the body’s non-specific response to cellular injury; the end result of highly amplified, yet tightly controlled, humoral and cellular mechanisms aimed principally at limiting tissue damage.

         

    Localized inflammation is an appropriate protective physiological response often eliminating the initiating noxious stimulus and restoring homeostasis. 

        

    Loss of local control or an exaggerated host reaction can, however, result in a progressive illness, the systemic inflammatory response syndrome [ SIRS], that in extreme cases, can lead to organ dysfunction and death.

        

    SIRS can result from many aetiological triggers [e.g. burns, infection, pancreatitis, and trauma] with sepsis defined as SIRS arising as a result of infection. 

         

    A co-ordinated immuno-inflammatory response requires the regulation of many cell types achieved principally by the actions of soluble protein [cytokine] and lipid or peptide [autocoid] mediators released by macrophages, neutrophils, lymphocytes, platelets, and the endothelium.

         

    Cytokins and autocoids regulate both the amplitude and duration of the inflammatory response. 

         

    In the attempt to control and localize an inflammatory process both pro- and anti-inflammatory mediators are simultaneously released. 

         

    An exaggerated anti-inflammatory response can result in immunosuppression, whereas an excessive pro-inflammatory response can produce systemic overflow of cytokines. 

         

    Serum concen trations of cytokines that do not accurately reflect local physiological levels. 

          

    The treatment of severe sepsis and septic shock has, until recently, centered around the eradication of established infection with surgery or antibiotics, accompanied by intensive organ support.

        

    With the realization that the pathological effects of sepsis and SIRS can result both from the direct actions of microorganisms and their toxins and indirectly from the host response, recent interest has been shown in novel immunomodulatory therapies. 

         

    Anti-cytokine therapies have attempted to either inhibit pro-inflammatory or enhance anti-inflammatory responses. 

         

    The interleukins are a class of cytokines produced by many different cell types. IL-1 and IL-8 have pro-inflammatory actions, whilst IL-4 and IL-10 have predominantly anti-inflammatory actions. 

         

    IL-1 is a key mediator in the immuno-inflammatory cascade, interacting closely with other mediator in the immuno-inflammatory cascade, interacting closely with other cytokines.

          

    Infusion of IL-1 in healthy volunteers produces clinical features of sepsis. Increased IL-1 levels have been recorded in patients with severe sepsis with levels often correlating with the severity of the inflammatory process. 

        

    Despite encouraging results from animal studies, no immunomodulatory therapy has to date been shown to produce an unequivocal reduction in mortality in large scale clinical sepsis trials.

          

    The therapeutic benefit to be obtained from immnumodulaltory agents in small and is unlikely to be realized in the absence of optimal resuscitation, surgery, antibiotics, and intensive care therapy.

          



 

   

Speciality Spotlight

   

   
Surgery
   

 

Immunomodulatory Therapies of Sepsis
         

  • S.J. Parkar P.E. Watkins
    Immunomodulatory Therapies of Sepsis and SIRS
    Recent Advances in Surgery-23, Year-2000
         
    Inflammation is the body’s non-specific response to cellular injury; the end result of highly amplified, yet tightly controlled, humoral and cellular mechanisms aimed principally at limiting tissue damage.
         
    Localized inflammation is an appropriate protective physiological response often eliminating the initiating noxious stimulus and restoring homeostasis. 
        
    Loss of local control or an exaggerated host reaction can, however, result in a progressive illness, the systemic inflammatory response syndrome [ SIRS], that in extreme cases, can lead to organ dysfunction and death.
        
    SIRS can result from many aetiological triggers [e.g. burns, infection, pancreatitis, and trauma] with sepsis defined as SIRS arising as a result of infection. 
         
    A co-ordinated immuno-inflammatory response requires the regulation of many cell types achieved principally by the actions of soluble protein [cytokine] and lipid or peptide [autocoid] mediators released by macrophages, neutrophils, lymphocytes, platelets, and the endothelium.
         
    Cytokins and autocoids regulate both the amplitude and duration of the inflammatory response. 
         
    In the attempt to control and localize an inflammatory process both pro- and anti-inflammatory mediators are simultaneously released. 
         
    An exaggerated anti-inflammatory response can result in immunosuppression, whereas an excessive pro-inflammatory response can produce systemic overflow of cytokines. 
         
    Serum concen trations of cytokines that do not accurately reflect local physiological levels. 
          
    The treatment of severe sepsis and septic shock has, until recently, centered around the eradication of established infection with surgery or antibiotics, accompanied by intensive organ support.
        
    With the realization that the pathological effects of sepsis and SIRS can result both from the direct actions of microorganisms and their toxins and indirectly from the host response, recent interest has been shown in novel immunomodulatory therapies. 
         
    Anti-cytokine therapies have attempted to either inhibit pro-inflammatory or enhance anti-inflammatory responses. 
         
    The interleukins are a class of cytokines produced by many different cell types. IL-1 and IL-8 have pro-inflammatory actions, whilst IL-4 and IL-10 have predominantly anti-inflammatory actions. 
         
    IL-1 is a key mediator in the immuno-inflammatory cascade, interacting closely with other mediator in the immuno-inflammatory cascade, interacting closely with other cytokines.
          
    Infusion of IL-1 in healthy volunteers produces clinical features of sepsis. Increased IL-1 levels have been recorded in patients with severe sepsis with levels often correlating with the severity of the inflammatory process. 
        
    Despite encouraging results from animal studies, no immunomodulatory therapy has to date been shown to produce an unequivocal reduction in mortality in large scale clinical sepsis trials.
          
    The therapeutic benefit to be obtained from immnumodulaltory agents in small and is unlikely to be realized in the absence of optimal resuscitation, surgery, antibiotics, and intensive care therapy.
          

 

By |2022-07-20T16:43:36+00:00July 20, 2022|Uncategorized|Comments Off on Immunomodulatory Therapies of Sepsis

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