Role And Modulation Of Kupffer Cells On The Production Of TNFα,IL-1β,IL-6 In Early Period Of Severe Burn Injury In Rats

Role and Modulation of Kupffer Cells on the Production of TNFα, IL-iβ and IL-6 in the early Period of Severe Burn Injury in Rats Background After severe burn injury, immune system is activated and large amount of inflammatory mediators are released to cause systemic inflammatory response which usually exists several minutes just after injury. Essentially, inflammation is a kind of protective reaction against etiological factors. Proper inflammatory reaction and proper amount of chemical mediators are beneficial to anti-impairment and tissue repair. However, the resultant systemic inflammation may develop into extensive tissue injury and multiple organ dysfunction when the primary insults (burn injury) are overwhelming or a second inflammatory insult (second hit) such as delayed resuscitation or sepsis triggers an exaggerated inflammation in positive feedback manner. Clinically, to treat hyper- inflammatory response resulting from severe burn injury, emphasizes the therapy of primary factors such as timely adequate fluid resuscitation, infection control, early excision of eschar etc. but no ideal methods has been used to stop inflammatory cascade by now. Strategically, measures should be taken to down-regulate activated immune response and decrease the release of inflammatory mediators. Therefore, it is of significance to study the source and modulation of inflammatory mediators after severe burn injury. Pro-inflammatory cytokines, TNFα, IL-iβ and IL-6 play a very important role in the occurrence and development of systemic inflammatory response. Abundant data from clinical patient and animal experiments show that, plasma level of these cytokines increase significantly in early period of severe burn injury. TNF a is the key to the cytokine network, which is the first to be released after trauma and can further induce the release of other cytokines and inflammatory cascade. External TNFα, IL-iβ can lead all symptoms similar to sepsis. IL-6 is the severe mediator to modulate acute phase reaction and result in hyper-metabolism after trauma. Histologically, macrophages are the severe source of TNFα , IL-iβ and IL-6. Kupffer cells constitute 80-90% of macrophages and reside at a strategic position in the hepatic sinusoid to filter the blood from portal vein. We don't know, however, what role Kupffer cells play in the production of pro-inflammatory cytokines after severe burn injury. It is indicated that, besides to bacteria and toxin, hypoxia, ischemia, foreign materials, tissue fragment, immune complex and inflammatory mediators can activate Kupffer cells, which later release cytokines, oxygen free radical, eicosanoid mediators, proteinase, nitric oxide etc. Those factors to activate Kupffer cells more or less exist after severe burn injury. Therefore, Kupffer cells may be a primary source of inflammatory mediators and play a very important role in the development of systemic inflammatory response. Being a second messenger for trans-membrane signal transduction, calcium ions play very important role in the activation of Kupffer cells. Lots of materials can induce the increase of [Ca2+]i in Kupffer cells. Inactivation of calcium ion channel can prevent some biological effects of Kupffer cells, such as the release of TNF, Platelet Activating Factor, oxygen free radical etc. It...