The Study On IL-11 And IL-11 Receptor Lever In The Blood Of Mouse With Chronic Idiopathic Thrombocytopenic Purpura

ObjectiveIdiopathic Thrombocvtopenic Purpura(ITP) or autoimmune thrombocvtopenic purpura,is a common hemorrhagic disease.The main manifestation includes hemorrhage,thrombocytopenia and dysmaduritic megakaryocyte of normal or increased amount in the bone marrow.Its incidence is 50～100/106 million,among which more than 50%are children.Children often present acute and self-limited cases.20%～25%patients developed into chromic cases,with mild and refractory clinical symptoms.The conventional therapy for chronic and refractory ITP(CITP) covers GCS,IVIG,IFN-,splenectomize,anti-D Ig and other immunosuppressants.But the curative effect is still unsatisfactory.Patients have to be transfused with PLT repeatedly because of hemorrhage.The expense is great but the duration is short.Meanwhile it brings the risk of hepatitis and HIV etc.IL-11,a key cytokine of ITP,has become a research focus recently.IL-11 is one of haematopoietic growth factors with pleiotropic effects on multiple tissues.It can induce the growth ofhematopoietic stem cells.Combined with IL-3 and SCF,it stimulates directly the proliferation of hematopotietic stem cells and induces megakaryocytes maturation resulting in increased platelet production.It also has biological activity on other tissues,including brain,spinal cord nervous,fat cells, et al.Since October,1997,the Food and Drug Administration approved rhIL-11 to be the first drug for increasing platelet production of patients with tumor following chemotherapy and radiation.A lot of researches proved IL-11 can use to treat chemotherapy-induced thrombocytopenia arising from marrow hypoplasia.It also enhanced leucocyte and erythrocyte.Recent years,some scholars get several curative effects by using IL-11 to treat ITP.Some research attest IL-11 can work on T cell and its receptor and restrain the production of IL-2,IFN-α,IL-6.It also can promote the hyperplasia of CD4+T cells,induce the maladjustment of Th1/Th2 which increased the incidence rate of ITP.Moreover,some studies discover that the levels of IL-11 in the blood are higher in the patients with CITP,which suggest that IL-11 maybe take a certain action in the mechanism of ITP.While the levels of IL-11 in the blood are higher in the patients with CITP,why are they using IL-11 to treat ITP ? Whether absenting of IL-11 or IL-11R in patients useless of treatment with IL-11 ? Further studies are needed to discuss the role of IL-11 and its receptor in the pathogenesis of chronic idiopathic thrombocytopenic purpura.So we induced the animal model of CITP,tested the level of their IL-11 and IL-11R,In order to assess whether absenting of IL-11 or IL-11 receptor and which will provide new theory to treat CITP.MethodsNinety(20±2 grams body weight) BALB/C mice were randomly dividedinto two groups:Group control(n=36) and Group CITP(n=54).Group control:Intraperitoneally inject NS 5mL/kg per one at the 1,3,5,7, 9,11,13,15,17 day.Group CITP:Intraperitoneally inject diluted APS(1:3) 5mL/kg per one at the 1, 3,5,7,9,11,13,15,17 day.Observation these items separately:1.Observed the clinical manifestation of mice.2.Taken blood to test blood routine by cutting trails at the zero and eighth day.3.Taken out eight mice in group control and twelve mice in group CITP randomly at the 8,11,14,17 day.Taken two tubes of blood via decollation.Use heparin to prevent cruor.One tube was used to test IL-11 receptor,while the other was used to test IL-11.4.Anatomized the third dead mice.(1) Weighed and observed the hemopoiesis of spleen.(2) Observe the megakaryocyte of marrow by light microscope.5.Observed the living or death of remain mice for one week.Results1.The clinical manifestation of miceGroup control was normal.Group CITP appeared different degree of spontaneous bleeding,and two mice died in anaphase.2.The change of blood routineTwo groups' blood routines had no change before injection.At the eighth day after injection,the platelet count of group CITP descended obviously,while the white blood cell and hemoglobin had no change.3.The level of IL-11 and IL-11RCompared with group control,the average level of IL-11 in group CITP increased at the 8,11,14,17 day,and was decreased step by step.The average level of IL-11R in group CITP also increased,but there were eleven mice had lower leverl of IL-11R.4.The weight and hemopoiesis of spleenThe weights of spleen had no difference in two groups and hemopoiesis deside marrow was unseen.5.The megakaryocyte of marrowThe megakaryocyte of marrow was normal in group control.The megakaryocyte of marrow in group CITP increased obviously and had maturation barrier.It's according with ITP marrow picture.6.The correlation between IL-11,IL-11R and bone marrow megakaryocyte in group CITP There was no correlation between the lever of IL-11 in the blood and bone marrow megakaryocyte counts.A significant positive correlation was found between the lever of IL-11 receptor in the blood and bone marrow megakaryocyte counts (r=0.77,r=0.84,p＜0.05).Conclusions1.Using APS to intraperitoneally inject into the mice could induce to set up the animal model of chronic idiopathic thrombocytopenic purpura(CITP).And its death rate was so lower that be convenient for experiment.2.The level of IL-11 in the blood of group CITP was increased and was decreased step by step.The level of IL-11R in group CITP also increased,but there were eleven mice had lower leverl of IL-11R.These suggested that IL-11 maybe take a certain action in the mechanism of CITP.3.There was no correlation between the lever of IL-11 in the blood and bone marrow megakaryocyte counts.A significant positive correlation was found between the lever of IL-11 receptor in the blood and bone marrow megakaryocyte counts.These suggested that we can get the message of the level of IL-11R in the blood by detecting bone marrow megakaryocyte counts.4.Further studies are needed to discuss the role of IL-11 and its receptor in the pathogenesis of chronic idiopathic thrombocytopenic purpura(CITP).