科研之友
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摘要
Tumour necrosis factor-alpha (TNF-alpha) has been shown to play a role in many inflammatory conditions. Currently anti-TNF-alpha drugs (e g. etanercept) are used in humans for treatment of autoimmune diseases In this study we aimed to elucidate the role of TNF-alpha in the development of virus-endotoxin-induced respiratory disease. Twenty-two caesarean derived colostrum deprived pigs were used. Initially, the availability in the lungs and circulation. and possible clinical and inflammatory effects of etanercept alone were assessed in 4 pigs after intratracheal and intraperitoneal administration of 0 5 mg/per route/per pig High anti-TNF-alpha activity was detected in bronchoalveolar lavage (BAL) fluids, peritoneal lavage fluids and serum of all animals for at least 8 h post-Inoculation (HPI) No clinical symptoms, lung lesions, lung cell infiltration or induction of IFN-alpha, IL-1, IL-6, IL-12 and TNF-alpha in BAL were detected Subsequently, the ability of etanercept to block porcine TNF-a and its effect on the above mentioned parameters and on lung virus titres were assessed in 8 pigs. They were Inoculated intratracheally with porcine respiratory coronavirus (PRCV) followed by lipopolysacchande (LPS) 24 h later. Etanercept was administered at the time of LPS inoculation via the same routes and dose as in the initial experiment. The parameters were compared with a control group (n = 8), receiving only PRCV-LPS. Half of the animals from each group were euthanized at 4 and the rest at 8 h after LPS inoculation. TNF-alpha was completely neutralized in 3 of the 4 animals euthanized at 4 HPI and significantly lower than in the PRCV-LPS group at all times. No significant differences in disease severity, lung lesions, virus replication, lung cell infiltration or levels of IFN-alpha, IL-1, IL-6 and IL-12/IL-23 were observed between the two groups. Blocking of TNF-alpha alone was not sufficient to ameliorate disease in the PRCV-LPS mode
- 出版日期2010-9-15
