Influence Of Immunity Response On ALI And MOF Following The Fire-aim Induced Aspiration And Its Mechanisms Of Action

The aim of our study was to analyze pulmonary innate and adaptive immune responses following the fireaim smoke inhalation-induced acute lung injury (ALI),and to study the influence of immunity response on ALI and MOF. Fireaim smoke inhalation-induced lung injury should be replicated at high(4000ppm) and low(2000ppm) does respectively in rats by repeating the model. After this period,lung tissue histopathology and four parsmeters of both treatment groups were to be observed compared to control animals: Change of Lung,liver,kidney and heart function, the phasic variations of concentrations of pro- anti- inflammatory cytokines in BALF, numbers of lymphocyte subsets in blood and BALF,and CD4+/CD8+ rate in BALF were determined by FCM.The main contents are divided into some sections as follows:1. The W/T ratio of rat lungs and contents of albumin and lactate dehydrogenase in bronchoalveolar lavage (BAL) increase with time. W/T ratio in the lung increased eventually and reached the peak at 6 hours later. Recovery did not occur after 24 hours. Lung histopathology of fire-aim-exposed animals revealed alveolar leakage characterizing ALI. The gross appearance and macropathology indicate that the lung injury has occurred. The bleeding was obvious at 4 hours, the edema reached the peak at 6 hours, and the recovery did not occur after 24 hours.2. Concentration of TNF-αincreases immediately after injury and reaches the peak value at 2h. Levels of IL-6 and IFN-γwere elevated followingly after 4h's injury and decreased at 12 h, whereas expression of IL-10 was increased at 12 h,and continuing upregulation to 24h. Cytokine is the direct medium for MOF that is triggered by TNF-αand causes the associated reaction of cytokine .TNF-αmay active pulmonary innate immune responses and contribute to the development of ALI. Concentration of TNF-αincreases immediately during the early period may contribute to enhance innate immune responses and active cell immune responses.Increased pulmonary concentrations of IL-6,IFN-γelicted by challenge can be explained by a significant accumulation of CD45+ non-lymphoid leukocytes comprising neutrophils and macrophage in the lung.Indeed,the change occurred in Cytokine concentration orchest anti- inflammatory.Factly,these important pro- inflammatory cytokines participant in and regulate innate immune response during the acture lung injury. Up-regulated expression of IL-6 in BAL enhanced intra-alveoal inflammation and protein leakage.Similarly, increased concentrations of IFN-γmay exacerbate ALI by the stimulation oxidative burst and ROS production from neutrophils as well as through increased IL-6 production by alveolar. Increases in IL-10 secretion IL-10 documented anti-inflammory immune response appeared to function ,whereas the upper control-lost IL-10 would be suggestive of possible suppressive effects in immune defense response and aggravated the development of MOF.The balance of Cytokines net play a important regulator in systemic immune response.In adaptive immune response ,the change in secretion of IL-6,IFN-γ,IL-10 may be a character as the effect on function.This may reflect the question as to the cellular source of these immunomodulatory cytokines.3. the numbers of lung-resident CD4+ and total T-lymphocytes were significantly reduced after challenge, and CD4+/CD8+ rate was decreased.ALI induced a significant apoptosis in CD4+ -and total T-lymphocytes which were very important in adaptive immune respones.This indicated that depletion of some lymphocytes demanded in adaptive immune response may lead to the decline of immune function.Reduction of CD4+ T- lymphocytes was associated with the decreased concentration of some key cytokine which could regulate immune respones.This may suggest that cell-mediated immune response in the lung had effect on both defense inflammation and eliecting immune injury in the lung tissue. In summary,These date suggest that fire-aim induced aspiration ALI is associated with exaggerated and sustained pulmonary innate immune responses partly by activated PMN and Mφ,whereas adaptive immunity in the lung is suppressed obviously.4. We have shown that CD8+ T-lymphocytes also participant in the development of lung inflammation and injury .It suggested that systemic cell-mediated immunity occurred in the development of ALI.With the appeaing of CD8+ T-lymphocytes,it can be concluded that nonspecific defense were not sufficient to control the development of SIRS.It may be a sign which indicates that specific immune response——cell-mediated immune response appeared to function.Thus, anti-inflammatory immune response effect function to defence inflammation in ALI by activating non-specific immune response. Anti-inflammatory mechanism depended on the development of adaptive T-lymphocytes response.5.We observed that aspiration at high dose (4000ppm) lead to more obvious increase in the numbers of neutrophils and decrease in the numbers of lymphocyte subsets in blood and BALF,and CD4+/ CD8+ rate in BALF rather than low dose(2000ppm).The decline of rate was likely due to immediate decrease in the numbers of CD4+ T- lymphocytes.Presumably,the demage of systemic immunory function related to the concentration of smoke inhalation.6.Concentration of ALT(alanine amino transferase), AST(L-asparate aminotransferase), URA, CRE(creatinine) and CK-MB(creatinekinase- MB) increase continually after injury. But we did not find the changes of liver,kidney and heart in macropathology. Although histological evidence of injury was demonstrated only in the lung,the biochemical evidence simultaneous liver,kidney and heart dysfunctionindicates that multiple organ dysfunction.Probably, the time to the changes occurind in histopathology were not long.Factly,both suppression of T cell-mediated immune and over-expression of innate immune response occurred in the last period of . The immune response response to the aspiration lead to a complex inflammatory cascade , lung injury and MODS rather than signal organ demange.