[Pulmonary immune responses to acute lung injury following smoke inhalation and its mechanisms].
OBJECTIVE
To analyze pulmonary innate and specific immune responses following the smoke inhalation-induced acute lung injury (ALI).


METHODS
Smoke inhalation-induced ALI should be replicated at high (4x10(-3)) and low (2x10(-3)) dose of carbon monoxide (CO) respectively for 24 hours. After this period, lung tissue histopathological changes and the parameters of both treatment groups were observed compared to those of control animals: the phasic variations of concentrations of pro-anti-inflammatory cytokines in bronchoalveolar lavage fluid (BALF), numbers of lymphocyte subsets in peripheral blood and BALF, CD45(+) lymphoid leukocytes, CD45(+) nonlymphoid leukocytes and CD4(+)/CD8(+) in BALF were determined by flow cytometry (FCM).


RESULTS
Lung histopathological changes of smoke-exposed animals revealed obvious alveolar leakage characterizing ALI. Concentrations of tumor necrosis factor-alpha (TNF-alpha) in BALF were increased immediately after injury and reached the peak at 2 hours after injury, and more obvious changes were seen in high dose group than those in low dose group. Levels of interleukin-6 (IL-6) and interferon-gamma (IFN-gamma) were elevated following after 4 hours injury peaking at 12 hours. The changes of levels of IL-6 in low dose group were more obviously than those in high dose group, and those of IFN-gamma were reverse. Levels of IL-6 and IFN-gamma were decreased at 24 hours, still higher than those of control group (P<0.05 or P<0.01), whereas the expressions of IL-10 were increased at 6 hours, and continuing upregulation to 24 hours compared with those of control group (P<0.05 or P<0.01). Additionally, the numbers of lung-resident CD4(+) T cells, CD8(+) T cells, natural killer cells, B cells and total T-lymphocytes in peripheral blood and BALF were significantly reduced after challenge (P<0.05 or P<0.01). The number of CD45(+) lymphoid leukocytes in BALF and CD4(+)/CD8(+) were decreased; while that of CD45(+) nonlymphoid leukocytes was increased obviously compared with those of control group, and obviously changed in high dose group than in low dose group (P<0.05 or P<0.01).


CONCLUSIONS
These data suggest that smoke inhalation induced ALI is associated with exaggerated and sustained pulmonary innate immune responses partly by activated polymorphonuclear neutrophils (PMN) and macrophage, whereas specific immunity in the lung is suppressed obviously.
Zhou
Min
M
Institute of Immunology, Anhui Medical University, Hefei, Anhui, China.
He
Jin-Sheng
JS
Li
Qing
Q
Li
Tao
T
Liu
Bo
B
Yan
Shang-Xue
SX
Lu
Chao
C
D055371:Acute Lung Injury / Q000209:etiology / Q000276:immunology* / Q000473:pathology; D000818:Animals; D001992:Bronchoalveolar Lavage Fluid / Q000737:chemistry / Q000276:immunology; D016516:CD4-CD8 Ratio; D004195:Disease Models, Animal; D005260:Female; D007371:Interferon-gamma / Q000378:metabolism; D016753:Interleukin-10 / Q000378:metabolism; D015850:Interleukin-6 / Q000378:metabolism; D008168:Lung / Q000473:pathology; D008297:Male; D011897:Random Allocation; D051381:Rats; D017208:Rats, Wistar; D015208:Smoke Inhalation Injury / Q000150:complications / Q000276:immunology* / Q000473:pathology; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism
D015850:Interleukin-6; D014409:Tumor Necrosis Factor-alpha; D016753:Interleukin-10; D007371:Interferon-gamma