Effects Of Agglutination On The Levels Of Complentment System And Cytokines In Rats

Influenza is caused by a highly mutated influenza virus,an acute complex respiratory infection.Different from the common cold,influenza is mainly manifested by severe systemic symptoms,including fever,cough,muscle pain and fatigue,etc.Severe patients may be complicated with pneumonia,viral myocarditis and nervous system infection,and even lead to acute lung injury,multi-organ dysfunction and other life-threatening conditions.However,the pathogenesis of acute lung injury and multiple organ dysfunction caused by influenza virus infection is still unclear.Studies have shown that severe influenza virus patients are accompanied by complement activation and cytokine storm.This excessive inflammatory reaction increases vascular permeability and induces acute lung injury and multi-organ dysfunction.There are two kinds of glycoproteins on the surface of virus particles,namely neuraminidase and hemagglutinin.Hemagglutinin is named for its ability to agglutinate red blood cells.It can be divided into plant hemagglutinin and viral hemagglutinin,both of them have different origins and molecular structures,but both of them can agglutinate red blood cells.Our previous studies have shown that hemagglutinin can induce agglutination in rats,leading to acute lung injury and multi-organ dysfunction.We speculate that agglutination may be involved in the pathogenesis of acute lung injury and multiple organ dysfunction caused by influenza virus.In order to prove this hypothesis,we injected phytohemagglutinin into rats to induce agglutination with erythrocytes,and explored the effect of agglutination on serum complement and cytokines levels.Objective:To investigate the effects of agglutination on serum levels of C5,C5 a,TNF-α,and IL-1β in rats.Methods:Forty-two healthy SD rats were randomly assigned to seven groups,namely: normal saline group,low-dose PHA group,medium-dose PHA group,high-dose PHA group,low-dose inactivated PHA group,medium-dose inactivated PHA group,and high-dose inactivated PHA group,with 6 rats in each group.The drugs were administered to rats individually through the tail vein.After 12 h,the contents of C5,C5 a,TNF-α and IL-1β in rat serum were determined by ELISA.Results:1.The content of C5 in serum of rats in low-dose,medium-dose and high-dose PHA group was(33.58±2.40)μg/mL、(32.55±5.09)μg/mL、(39.98±8.30)μg/mL,all significantly higher than that in normal saline group(27.26±1.30)μg/mL,and the corresponding concentration of inactivated PHA group(28.01±0.87、26.67±1.66、27.00±1.73)μg/mL,the difference was statistically significant(P< 0.05).2.The contents of C5 a in serum of rats in low-dose,medium-dose and high-dose PHA group were(13.18±1.70)μg/mL,(14.39±3.21)μg/mL,(17.71±4.88)μg/mL,which were significantly higher than those in normal saline group(10.49±0.45)μg/mL and inactivated PHA group(11.45±1.76、10.43±0.28 、 10.40±0.35)μg/mL,and the differences were statistically significant(P < 0.05).3.TNF-α contents in serum of rats in low-dose,medium-dose and high-dose PHA group were(30.57±0.88)pg/mL,(32.61±2.34)pg/mL,(33.68±2.98)pg /mL,all significantly higher than that in normal saline group(28.45 0.93)pg/mL and inactivated PHA group(29.04±1.43、28.32±3.44、28.98±1.98)pg/mL,with statistically significant differences(P < 0.05).4.Serum IL-1β contents of rats in low dose,medium dose and high dose PHA group were(77.85±12.85)pg/mL、(90.60±8.55)pg/mL、(194.36±69.30)pg /mL,all significantly higher than that in normal saline group(58.42±4.78)pg/mL and inactivated PHA group(60.32±13.98、59.29±5.82、60.52±11.25)pg/mL,with statistically significant differences(P < 0.05).Conclusion:Agglutination activate the complement system and causes a "cytokine storm",which may be one of the pathogenic mechanisms of acute lung injury and multi-organ failure after influenza virus infection.