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Sepsis Syndrome: New Insights into its Pathogenesis and

Treatment

Lateef A. Olopoenia, M.D.*

(*Medical Director, Liberty Medical and Research Centre, Lagos Nigeria)

Sepsis is a well-recognized complication of serious infection with pathogenesis and pathophysiology that are poorly understood. While sepsis, sepsis syndrome and septic shock maynot be separate disorders; they represent severe stages of the same disorder. Just as the

 pathogenesis of sepsis is very complex, involving interactions of a large number of endotoxininduced endogenous mediators, so is the understanding and clinical applications of the mediatorscomplex in management of septic patients. Half a century of research has shown that most of theendotoxin's toxic effects are indirectly involved in the pathogenesis of sepsis, and that a numberof endotoxin-inducod endogenous molecules participate directly in the pathogenesis of the sepsissyndrome. It has thus become apparent that the initiating event in the sepsis cascade is the releaseof the endotoxin into the systemic circulation. While the sepsis cascade can become self-

 perpetuating event,1  a host of new treatment modality that can interrupt this cascade at  one or

more places are being developed. Studies have shown that exclusive reliance on antimicrobialagents alone is unlikely to improve the outcome of the sepsis condition to any substantive degree.Among the most important of the endotoxin-induced mediators that have been studied adequatelywith some clinical application include tumor necrosis factor (TNF), interleukin-1, -2 , and -6 (IL-1, IL-2, and IL-6) , and platelet activating factor (PAF).

2,3 As complex as the pathogenesis of the

sepsis may seem, its study offers insights into new treatment modalities. Until recently, treatmentavailable for septic patients had been antibiotics and supportive care (mechanical ventilation andfluid administration). Data from the use of specific monockmal antibodies to several of theendogmous cascade substances in sepsis syndrome has been very encouraging. While furtherstudies are in progress on other cytokines, current treatment modalities attempt to incorporateanti-cytokine specific monoclonal anti-bodies into treatment of sepsis.  [Phil J Microbiol Infect Dis

1996; 25(2):S7] 

References1. Bone RC. Pathogenesis of Sepsis. Ann Intern Med1991; 115:457-569,2. Dinarello CA, Mier JW. Lymphokines. N Engl J Med 1987; 317:940-945,3. Jacobs RF , Tabor DR. Immune Cellular Interactionsduring sepsis and septic injury. Crit CareClin 1989; 5:9-29,