Innate Immune System in Sepsis Immunopathogenesis and Its Modulation as a Future Therapeutic Approach

Immune system plays an important role in the development of systemic as well as compartmentalized inflammation though it may arise due to the various causes i.e. infection, trauma, burns, hemorrhagic pancreatitis and immune-mediated tissue injury. Pathogenic as well as commensal microorganisms evoke an immune response if they, or their constituents, pass the barrier between the external and internal environment. After recognition of the bacteria or their products, body launches an attack, kills the bacteria, and repairs putative damage. This sequence of events is highly regulated, enabling the body to combat infection by a tailor-made mechanism that is potent enough to eradicate the pathogen but not so potent as to cause unnecessary damage to the body. But, when this regulated immune mediated defense mechanism against the invading pathogenic bacteria gets deregulated then it causes harm to the body’s own organs and leads to the development of the particular organ specific damage (compartmentalized inflammation) or the development of systemic inflammatory response syndrome (SIRS) or the sepsis. Accordingly, acute inflammation is a self resolving property of immune mediated reaction and is a highly regulated cascade of events (Khatami, 2011). These events were recently described as ‘Yin’ (i.e. apoptosis, pro-inflammatory molecules etc.) and ‘Yang’ (i.e. wound healing, antiinflammatory, resolution phase etc.) phenomenon with an intimate involvement of vascular components (Khatami, 2008; Khatami, 2009). For example, in severe acute inflammatory conditions like sepsis, which is mediated by cytokine storm or pneumonia the causative agents bypass normal host immune response activated in the form of acute inflammation by first damaging the blood vascular system integrity and then gain access to different compartments of the body and induce excess production of pro-apoptotic as well as tissue damaging molecules (i.e. TNF-┙, various interleukins, and free radicals) (Khatami, 2011). These molecules are potent enough for damaging and shutting down the immune-tissue interaction leading to enhanced tissue damage and in case of sepsis, development of multi organ failure, septic shock and ultimately death of the patient (Khatami, 2011). According to the nomenclature, SIRS associated with a documented infection is sepsis. To date, most studies of the etiology and outcome of SIRS have focused on severely ill patients treated at intensive care units (Davis and Wenzel, 1995; Rixen et al., 1996; Headley et al., 1997; and Bonten et al., 1997). Sepsis/SIRS and septic shock originated due to gram negative or gram positive bacterial infection or caused by other pathogens like fungi, parasites or