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Arch Hellen Med, 19(6), November-December 2002, 614-625


The pathogenesis of sepsis syndrome and the role of immunomodulation

1Department of Internal Medicine
2Section of Infectious Diseases, University of Patras, School of Medicine, Rion, Patras, Greece

Despite important advances in critical care medicine the mortality rate of sepsis syndrome remains high. Sepsis is an inflammatory response of the immune system to bacterial infection. The clinical course of sepsis syndrome ranges from physiological derangements to severe multiple organ dysfunction and death. The pathogenesis of sepsis syndrome is still not completely understood. The host defense mechanisms against the lipopolysaccharide of Gram-negative and the peptidoglycan of Gram-positive bacteria involve polymorphonuclear and mononuclear phagocytes, natural killer cells and B- and T-lymphocytes. The role of complement and of the endothelium is essential in immune defense. Recent studies have shown that sepsis is a biphasic entity, the early phase being characterized by the systemic release of pro-inflammatory cytokines, such as tumor necrosis factor-α (TNFα) and interleukin-1 (IL-1). Proinflammatory mediators help recruit macrophages, lymphocytes, platelets and coagulation factors to the site of infection. In the late phase, anti-inflammatory mediators, such as interleukin- 10, may be released in an effort to counteract ongoing inflammation. Excessive release of anti-inflammatory mediators may result in immunosuppression. The expression of the major histocompatibility complex class II (HLA-DR) on monocytes in patients with sepsis could constitute a useful indicator of the immunological status of the host. Recent, clinical trials aiming to down-regulate the pro-inflammatory mediators have proved to be rather disappointing, but new immunomodulatory agents are under investigation. The use of immunoglobulins, growth factors, monoclonal antibodies against endotoxin or TNFα, nitric oxide (NO) and platelet activating factor (PAF) inhibitors and interleukin-1 receptor antagonists (IL-ra) have been studied in septic patients. Immunological intervention based on individual monitoring of the immune status in septic patients holds promise for the effective immunomodulation of sepsis.

Key words: Cytokines, Immunomodulation, Pathogenesis, Sepsis.

© Archives of Hellenic Medicine