The Change Of CD86 On Monocyte After Thermal Injuries And Its' Relationship With Inflammation

The Changes of CD86 on the Surface of Monocyte after Burns and its' Relationship with systemic inflammation1.Introduction:Problems in systemic inflammation is the primary cause of multiple organ failure (MOF) for burned patients.Terefore,how to control systemic inflammation reactions and reduce multiple organ failure is the main topic in the treatment of thermal injuries patients.Systemic inflammation is divided into several groups:the first is systemic inflammatory response syndrome(SIRS),which can be diagnosed by heart rate,breath frequency,body temperature and quantitative change of white blood cell et al. Another is compensatory anti-inflammatory response syndrome(CARS),and its' clinical diagnostic criteria is according to immune indexes and it's characterized by depression of immune function.If SIRS and CARS exist at the same time,it is called mixed anti-inflammatory response syndrome(MARS).Disfuction of immune after bums is the main cause for tissue injury and susceptibility to infection.Monocyte is one of the important immune cells,which can be adjusted in order to adapt to the change of microenvironment according to multiple signals from intracellular and extemal matrix.When simulated by endotoxin and the IFN-R, monocyte will differentiate into type M1,which not only can kill invasive microorganism,but also can recruit and activate immune effect cell.When simulated by IL-4 and IL-13,monocyte will differentiate into type M2,which favors the blood vessel regeneration in the tissue,and reduces the inflammation response.Thus we can leam more about immune function in terms of changes of molecular markers on the surface of monocyte.It's believed that costimulation signals are very important to T cell activation, because the loss of costimulation signals will lead to anergy of T cell.CD86 is the ligand of CD28/CTLA-4 on antigen presenting cell(APC)and has important functions. By monitoring CD86 on the surface of monocyte,and other immune indexes,we can judege the prognosis of bumed patients.There are so many proinflammation mediators(such as INF-R,1L-2,IL-1,IL-6, IL-12,IL-8 et al) and anti-inflammation mediators(such as IL-10,IL-4,IL-13,IL-1ra) that we can judge the state of patients by monitoring changes of some kind of mediators.It is believed that we can judge immune function by T leukomonocyte especially Thl and Th2,the change of which can reflect the balance of SIRS/CARS, and IFN-R is regarded as one of immune index,but because of their multiple and biological function complexity,biological significance of IFN-R and IL-4 are suspected.According to clinical diagnostic criteria of SIRS,a patient who suffers severe thermal injuries is in the state of SIRS for almost 28 days in the first month,but it is unable to know that immune state is excessively activitived or depressed.Monocyte is important immune cell,but we can't know the immune state according to change of monocyte's function.It is not reported that we can distinguish SIRS from CARS by the function of monocyte too.The aim of this study is to figure out the relationship among the change of CD86 on the surface of monocyte,cytokines and inflammatory reaction in order to we can find some useful variables to guide our clinical treatment.2.Objectives:(1) To study the change of CD86 on the surface of monocyte after thermal injury.(2) To study the change ofcytokines after thermal injury.(3) To study the correlation between the change of CD86 on monocyte,cytokines and inflammation.3.Materials and Methods:PartⅠthe Change of CD86 on the Surface of Monocyte from Burning Patients at Different Time pointsA total 28 participantes were selected randomely in this study.14 Burn victims admitted to bum unit at changhai hospital were prospectively included in the study. Exclusion criteria included all patients younger than 18 years and older than 65 years and with total bum surface area(TBSA) injury＜30%.14 normal people were chosen as contrast.Blood samples were drawn from patients in the following time points after thermal injury:Day 1,3,5,7,10,14.If sepsis happened,we increased the frequency of measurement.Flow cytometric expression of CD86,Mean Fluorescent intensity (MFI) of CD86 and HLA-DR were assessed on peripheral blood.Staining and cell acquisition on flow cytometer were performed within 2 hours after blood sampling.Monoclonal antibodies(CD14,CD86,HLA-DR)were used according to the manufacturer's recommendations.Results were expressed as percentages of CD86 positive monocytes of total monocyte population.We divided the patients into two groups by Abbreviated Bum Severity Index(ABSI),one group's ABSI is more than 50 and the other's is less than 50.Phase after burns is divided into four parts by 1-3 day,5-7 day,10-14 day,and more than 20 day.Not only we can compare two groups, but also we can compare the CD86 values at different time points.PartⅡChange of Inflammation Mediators(CRP,IL-1β,IL-6,IL-8 and IL-10)at different time points after Buring.EDTA-anticoagulated samples were drawn in the following time points after thermal injury:day 1,3,5,7,10,14.If sepsis happened,the frequency of sample measurement increased.Plasma levels of CRP,IL-1β,IL-6,IL-8,IL-10 were measured by the method of commercial enzyme-linked immunosorbent assay kits(ELISA),according to the manufacturers' recommendations.The normal values were also measured.The changes of cytokines after bums are observed.Statistical analysis:All statistical analysis was done by SPSS software packages.(version 10.5.1).The normal plasm range of CD86 expression was calculated as the mean±1.96SD,The level of CD86 was compared between patiens and healthy control participants by the method of nonparametric Mann-Whitney U test(two-tailed)at the signifianct level ofα= 0.05.Spearman's rank correlation coefficient was calculated and tested for significance(two-tailed).A p value＜0.05 was regarded as significant without correction of the number of tests performed.4.ResultsPartⅠCD86 and MFI of CD86 decreased a lot in the patients who suffer severe burns. They reached low point at 1-3 day,and elevated after the first week.It is significant. Inhalation has effect on expression of CD86.CD86 has positive correlation with HLA-DR and MIF,The cytokines increased and CD86 decreased a lot when the patients suffered from heart failure,lung edema,or sepsis.PartⅡIL-1β,IL-6,IL-8,IL-10 and CRP were all elevated at the early stage of thermal injury,and reached peak at the end of first week after burns,The cytokines increased and CD86 decreased a lot when the patients suffered heart failure,lung edema,and sepsis.There is no correlation between two groups.CD86 has negative correlation with IL-10 and has no correlation with IL-1β,IL-6,IL-8 and CRP. There are no correlation between CD86 MFI and cytokines.5.Conclusions:(1) At the early stage of burns,CD86 on the surface of monocyte decreased a lot which is related with immune statues,so it is a helpful variable for clinical treatments and prognosis.(2) At the early stage of bums,IL-1β,IL-6,IL-8,IL-10 and CRP are elevated a lot,they are related with immune state of patients and can act as immune variables to guide our clinical treatments.