Multiple Organ Dysfunction Syndrome - Etiology

Etiology

The condition usually results from infection, injury (accident, surgery), hypoperfusion and hypermetabolism. The primary cause triggers an uncontrolled inflammatory response. In operative and non-operative patients sepsis is the most common cause. Sepsis may result in septic shock. In the absence of infection a sepsis-like disorder is termed systemic inflammatory response syndrome (SIRS). Both SIRS and sepsis could ultimately progress to multiple organ dysfunction syndrome. However, in one-third of the patients no primary focus can be found. Multiple organ dysfunction syndrome is well established as the final stage of a continuum Systemic inflammatory response syndrome + infection sepsis severe sepsis Multiple organ dysfunction syndrome. Currently, investigators are looking into genetic targets for possible gene therapy to prevent the progression to Multiple organ dysfunction syndrome. Some authors have conjectured that the inactivation of the transcription factors NF-κB and AP-1 would be appropriate targets in preventing sepsis and Systemic inflammatory response syndrome. These two genes are pro-inflammatory. However, they are essential components of a normal healthy immune response, so there is risk of increasing vulnerability to infection, which can also cause clinical deterioration.

Some have developed a mouse model sepsis via cecal ligation and puncture (CLP). Male Balb/c mice subjected to CLP were given an IL-10-carrying vector or an empty control vector. Lung, Liver and kidney tissue destruction were measured by assessing myeloperoxidase and malonialdehyde activity. These last two are endogenous oxidizing compounds produced during tissue inflammation. The authors assessed the level neutrophil infiltration in lung and liver tissue. IL-10 protein expression was measured using immunohistochemistry. The expression of Tumor necrosis factor-alpha mRNA was measured at 3,8, and 24 hours after CLP using reverse transcription polymerase chain reaction. Their results show significantly reduced organ damage by IL-10 gene transfer, as quantified by reduced myeloperoxidase activity in the lung, liver, and kidney. The malonialdehyde level was not affected by the transfer into the liver. The livers of the mice infected with the adenoviral vector showed reduced neutrophil activity. The lung and kidney samples in mice carrying the gene showed lower expression of Tumor necrosis factor-alpha mRNA. The investigators concluded that increased IL-10 expression significantly reduced sepsis-induced Multiple organ injury.