The Clinical Significance Of Altered IL-22and IL-37Serum Level During The Course Of Guillain-barre Syndrome

Background and ObjectivesGuillain-Barre syndrome (GBS) is a common multiple spinal nerves and peripheralnerve demyelinating disease by humoral and cell-mediated immune joint,also knownas symmetric multi-radiculitis or acute idiopathic polyneuritis.Clinical manifestationsof sensory dysfunction progressive increase in symmetry paralysis,flaccid paralysis oflimbs,as well as varying degrees of sensory dysfunction.Cytokines play as a role tostart, maintain and regulate in autoimmune injury,more and more scholars areconcerned about the role of cytokines in animal models of GBS and its ENA.Thelarge number of experimental studies have shown that:development and outcome ofautoimmune diseases is run by pro-inflammatory cytokines and inflammatorycytokine which mediated suppression of changing the balance of Th1/Th2cells.Interleukin-22(IL-22) is one of the IL-10cytokine family which was recentlydiscovered,NK cells,γδT cells,LTi cells,Th17cells and Th22cells can produceIL-22,and Th17cells are CD4+T effector cells which can secrete various cytokines,asIL-2,IL-17A,IL-17F and IL-22.In the mouse model of Experimental Autoimmune Encephalitis (EAE),the levels of IL-17mRNA and proteins increase,IL-22and IL-17in a variety of animal models and vitro tests can be confirmed mutually cooperatingto participate in pro-inflammatory immune response,and,in tumor cells,IL-22caninducehaptoglobin,serum amyloid,α1antichymotrypsin and other acute phaseprotein.Interleukin-37(IL-37) is one of the cytokines IL-1family members,IL-37expression in macrophages or epithelial cells,it can inhibit the TLR-inducedpro-inflammatory produce and release of cytokines IL-1α,IL-1β,IL-18,IFN-γ,TNF-αand the activity of dendritic cell,also can promote the expression of CD4+CD25+regulatory T cells,which inhibit the immune response effectively.In our research,ourintent is to investigate the function of IL-22and IL-37in GBS by detect the serumconcentration of IL-22and IL-37during the different stages of GBS.And providefurther rationale for a new treatment of GBS.Materials and MethodsCollect between September2012and February2012in the first affiliated hospitalof zhengzhou university neurology hospital, a total of51patients with GBS.Including30male patients and21female patients,from8to74years,average age is(42.00±18.23) years.All GBS patients was selected through the department ofneurology of two or more doctors ask for details of the history, the physicalexamination of the nervous system and muscle emg examination and cerebrospinalfluid examination.Then the severity of all patients enrolled Hughes score to evaluatethe disease.Choose31healthy volunteers to be the healthy control(HC) group duringthe same period in our clinic examination.There are19males and12females,from8to66years,average age is (40.61±18.23) years,without recent history of infectiousdisease,history of allergic diseases,cardiovascular diseases,cancer and autoimmunedisease history.They all not have surgery,use the drugs such as immunosuppressive agents, hormones, immunoglobulins and other drugs affect the immune systembefore draw off blood.The experimental group and the control group of age and sexdifference was not statistically significant.Patients and healthy control group involvedin the study were informed of the purpose of the experiment, participants agreed theconsent and signed informed consent.All patients and healthy people need to be fasting before draw off blood more thanl0hours,draw off blood from cubital vein in next morning,stay in the room10to20minutes before centrifugal,and all the sample was preserved at the temperature of-80℃.GBS patients’ venous blood samples were collected in the acute phase(onsetl-14) days and convalescence(onset30to60days).Healthy control group collectedblood samples only once.ELISA measured was used to test the levels of IL-22andIL-37in serum.All data was statistically analyzed by using SPSSl7.0.Quantitativedata were presented as mean±standard deviation (x±s),quantitative data werecompared with two groups use two independent samples t-test,two sets ofquantitative data were analyzed by using spearman correlation coefficientanalysis,quantitative data were compared with multiple sets use single-factor analysisof variance and pairwise comparisons (LSD test).P<0.05,so the difference wasstatistically significant.Result1.The concentration of IL-22in serum both in the acute(110.70±24.37)ng/L andresume(78.32±11.68)ng/L phase of GBS patients are elevated significantlycompared to the healthy control(75.62±15.00)ng/L groups,while the serum level ofIL-22are up-regulated more significantly during the acute stage than the resume stage. 2.The concentration of IL-37in serum both in the acute(62.80±9.29)ng/L andresume(84.38±6.67)ng/L phase of GBS patients are elevated significantly comparedto the healthy control(57.82±16.11)ng/ml groups.While the serum level of IL-37areup-regulated more significantly during the resume stage than the acute stage.3.The concentration of IL-22in serum in the acute phase of GBS patients aresignificantly associated with the Hughes score; the concentration of IL-37in serum inthe acute phase of GBS patients show no significant correlation with Hughes score.4. The concentration of IL-37in serum in the resume phase of GBS patients aresignificantly associated with the Hughes score; the concentration of IL-22in serum inthe resume phase of GBS patients show no significant correlation with Hughes score.5.The demyelinating+axonal subgroup(141.13±23.45)ng/L of GBS patients showshigher serum level of IL-22during the acute phase than the axonal subgroup (108.41±9.25)ng/L and demyelinating subgroup(90.45±3.62)ng/L;the concentration ofIL-37in serum shows no significant difference among the demyelinating+axonalsubgroup,axonal subgroup and demyelinating subgroup.6.The demyelinating subgroup(90.10±3.72)ng/L of GBS patients shows higherserum level of IL-37during the resume phase than the axonal subgroup (84.44±3.06)ng/L and demyelinating+axonal subgroup(75.52±3.30)ng/L;the concentrationof IL-22in serum shows no significant difference among the demyelinating+axonalsubgroup,axonal subgroup and demyelinating subgroup.Conclusion1.IL-22in the acute phase of GBS patients with recovery expression level in theserum were significantly increased than the control group, IL-22May participate inGBS immune response. Acute phase of GBS patients IL-22level recovery increased more significantly, consider possible IL-22major proinflammatory role in immuneresponse to the starting phase.2.IL-37in the acute phase of GBS patients with recovery expression level in theserum were significantly increased than the control group, consider IL-37Mayparticipate in GBS immune response. GBS patients recovery level of IL-37acutephase increases more significantly,37May consider IL-mainly in the suppression ofinflammatory disease recovery.3. The concentration of IL-22in serum in the acute phase of GBS patients waspositively correlated with the severity of the disease;the concentration of IL-37inserum in the resume phase of GBS patients was negative correlated with the severityof the disease.4.The concentration of IL-22in serum in the acute phase of GBS patients may beinvolved in the damage of myelin and axonal,the concentration of IL-37in serum inthe resume phase of GBS patients may be involved in the recovery of myelin andaxonal.