Effect Of Anti-rat IL-6R Monoclonal Antibody On Acute Lung Injury Induced By LPS At Early Stage In SD Rat

Objective:To investigate the effects of Anti-rat IL-6R monoclonal antibody on acute lung injury(ALI)induced by LPS at early stage in Rat and to observe the changes of IL-6,TNF-α,NF-κB. Compare the anti-inflammatory and therapeutic action between Anti-rat IL-6R monoclonal antibody and corticosteroids in ARDS models.Methods:40 SD Rats were randomly divided into 5 group(s8 Rats each group). The control group(GroupA)was given normal saline(0.9ml/kg) 1ml intra-peritoneally;ALI group(Group B)was induced by LPS (8mg/kg BW) given intra-peritoneally with 1/10 LPS before research and the rest LPS was given 12h later.ALI+dexamethasone group(Group C), the Rats received intraperitoneal injection of dexamethasone (2mg/kg BW ) while administration of LPS on the second time .ALI+Anti-rat IL-6R monoclonal antibody group(Group D):the SD Rat received intraperitoneal injection of Anti-rat IL-6R monoclonal antibody (200μg /kg) while administration of LPS on the second time .ALI+Rabbit IgG group(Group E):the SD Rat received intraperitoneal injection of Rabbit IgG (200μg /kg) while administration of LPS on the second time. Four hours later, the rats were put to death. Bronchoalveolar lavage was administered in the left lung. Two lobes of the right lung were selected and weighed after stoving, one of which was made as pathological specimen and examined in a series of indexes respectively, such as wet/dry weight(W/D), total cell count of Bronchoalveolar lavage fluid(BALF), differential count of neutrophils, as well as change of protein level; content of IL-6 and TNF-αin serum and BALF was also measured with ELISA(enzyme linked immunosorbent assay). Comparison of pathological change was made with light microscope and blind score and change of expression of IL-6, TNF-αand NF-κB was monitored in immunohistochemical method.Results:(1) In the groups of ALI(B group) and ALI+IgG(E group), the total leukocytes, numbers of PMN were higher than those of the control group(P<0.05). Compared with ALI group, the percentage of PMN decreased in ALI+ dexamethasone group(C group)and ALI+Anti-IL-6R group(D group)(P<0.05).(2) In the groups of ALI (B group) and ALI+IgG(E group), the protein concentration in the BALF and W/D were higher than those of the control group (P<0.05).But the protein concentration in ALI +dexamethasone group(C group)and ALI+Anti-IL-6R group(D group)was lower than ALI group (B group) and ALI+IgG group (E group).(3) In serum and BALF of both of ALI group (B group) and ALI+IgG group (E group), the concentrations IL-6 and TNF-αwere significantly higher than NS group (P<0.05). There was no difference among ALI (B group),ALI+IgG (E group) and ALI+Anti-IL-6R(D group)(P >0.05).The results with light microscopy (LM) showed that ALI(B group) and ALI + IgG(E group) manifested with acute and diffused alveolar damage including necrosis of the endothelia and epithelia, leukocyte accumulation in lung tissue, pulmonary edema ,profound lung inflammation. All the above histological changes induced by LPS were attenuated by dexamethasone and Anti-IL-6R.Conclusion:1.Anti-rat IL-6R monoclonal antibody could inhibit permeation, accumulation of neutrophils in the lung,and lessen edema and hemorrhage of interstitium and alveolies in Rat ALI model induced by LPS . 2. Anti-rat IL-6R monoclonal antibody has no impact on the concentration of IL-6,TNF-αin serum and BALF. 3. Anti-IL-6R monoclonal antibody could down-regulate NF-κB expression in lung tissue. In conclusion, Anti-IL-6R monoclonal antibody could play an role in the protection of ALI model, however, it doesn't influence the concentration of IL-6,TNF-αin serum and BALF but expression of NF-κB and IL-6 in lung tissue.