Study Of Ivermectin Effect On Inflammatory Reaction Induced By Lipopolysaccharide

The present study aimed to investigate the effect of ivermectin on mortality endotoxemic mice which induced by lipopolysaccharide, the mechanism of its action. lipopolysaccharide (LPS), a componentof the gram-negative bacterial cell wall, induces the disturbance of immune and inflammatory responses and causes extensive tissue damage. Cytokine is the main mediator in the earlier period of sepsis. Another purpose is to investigate the serum cytokine concentration to study that ivermectin protect lipopolysaccharide induced sepsis mechanism. In the study of sepsis animal model of lipopolysaccharide indicate that IL-1β, IL-6, IL-10, TNF-αplay a important role in the therapeutic procedure. The last purpose is evaluate the protective effects of Ivermectin on mice with endotoxic.First we intragastric administration ivermectin to C57 mice, and injection lipopolysaccharide to C57 mice to made endoxemia model for the protection action. We look for the best effect dosage for ivermectin. After that we use enzyme linked immunosorbent assay to study serum of LPS mice found that cytokine have markly change the cytokine concentration. Mices model of endotoxic was produced in the study. The mice were randomly divided into the normal control group ( group A ,n=9 ), endotoxic group (group B,n=9 ), Ivermectin treatment group (group C, n=9), The normal control A group of mices Were administrated intragastrcally with saline, Bgroup of mice were administrated with lipopolysaccharide (LPS, 600ug/kg, ip), C group of mice were administrated with Ivermectin (2mg/kg) and LPS, which were administrated after the Ivermectin. of 60min, each group of mice were put to death by the time 6 h, 12h, 24h, adopted tissue of duodenum, lung, heart, liver and spleen were put 10%neutral formalin solution to fix make Waxing slice, HE dyeing, observe the tissue under light microscope.We study the sepsis mice and intragastric administration ivermectin conclude that could protect animal from this disease. Pretreatment with 2mg/kg ivermectin significantly decreased the mortality rate and attenuated tissue injury in mice challenged with LPS. After 48 hour challenged by LPS, control team survival rate is 0%, but ivermectin team is 50%. This study demonstrate the protection role of ivermectin.Different ivermectin team also have distinction survival rate. The lower dosage team survival rate is 40% in 36 hour, at that time middle and higher team are all 80%, which was significantly better han that of mice exposed to LPS (P<0.01 or 0.05). In this study we also found middle dosage have the best therapeutic action.We use enzyme linked immunosorbent assay to study serum of LPS mice found that cytokine have markly change the cytokine concentration. LPS induce TNF-αconcentration in serum on 1 hour,control 84.0ng/ml ivermectin team 50.0ng/ml. Ivermevtin could suppress TNF-αincreasing. TNF-αcould be a key factor which determine thareputic procedure of sepsis. So we conclude that ivermectin have therapeutical effect on sepsis.Ivermectin suppress IL-1βsecrete and prolong it peak time, control team is 750ng/ml compared with ivermectin team 450ng/ml, this attenuate LPS originated blood pressure degression, COX production,platelet-activatingfactor, NO proinflammatory substance release, and relieve general inflammatory reaction cause by LPS. Ivermectin could also decrease IL-6 peak concentration.IL-10 lessen LPS caused fever, play a suppress role in TNF, IL-6, IL-8 secrete and neutrophile granulocyte aggregation and degranulation. Ivermectin efficiently accelerate IL-10 release rate. In 1 hour control team IL-10 concentration is 4100ng/ml compared with ivermectin team 6400ng/ml. Ivermectin made IL-10 peak concentration corresponding with TNF peak concentration, to protect general Inflammatory reaction from TNF-α.A group of mices were normal ,B group of mice were show Small intestinal bleeding, cellular necrosis, generous fragment in enteric cavity at 6h, 12h. At the time 12h 24h, alveolar space with inflammatory cell infiltrate. Angiotelectasis to bleed, licer cells of granular degeneration, the tissue of lung, bowels, liver were serious damaged at the time 24h.the hearts have a little of injury, the spleen were not influenced in the study. C groups were such a little pathological change than B groups. The result s suggest that Ivermectin has benefit effects on alleviating inflammation, and can prevent visceral organ damages in mices with endotoxic.