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Serum Levels Of MCP-1 And Interleukin-12p40 In Children Infected With Mycoplasma Pneumonia

Posted on:2008-08-04Degree:MasterType:Thesis
Country:ChinaCandidate:M Y TuFull Text:PDF
GTID:2144360212996878Subject:Academy of Pediatrics
Abstract/Summary:PDF Full Text Request
Mycoplasma pneumonia(MP) is a nontypical pathogen between virus and bacteria,which is familiar in recent years.It can cause a spectrum of human acute and chronic diseases,ranging from respiratory and genitourinary tract ifections to central nervous system and joint pathologies. The state of illness in some infected patients can be deferred or changed into chronic,and simply antibiotic treatment is not enough.As a result, the pathogenesis has become a hotspot research in recently.These days the nosogenesis of MP cover as follows:first,the direct injure from the pathogen adherence to host cells;secondly,the toxinum such as peroxide released from pathogen and the third is immune impairment.It is thinking that immunological mechanism has play an important role in extrapulmonary injury induced by MP,which has not been clarified.Autoimmune diseases usually present with Th1 ascendant,while allergic diseases show a major function of Th2 cell immunity.Although researchs at present show a existence of a turbulence function between Th1 and Th2 when infected with MP,which one plays dominating is still unclear. Scholar overseas consider it is Thl,while most people internal think it is Th2,as people internal found cytokine IFN-γdelegated of Th1 fall and IL-4 delegated of Th2 elevate. IL-12 is a cytokine which can influence the polarization of lymphocytes from Th0 to Th1.The bioactivity of IL-12 is mediated by heterodimers of disulfide-linked p35 and p40 protein subunits that interacts with a high affinity receptor on lymphocytes to transduce activating signals.Specifically,IL-12 triggers IFN-γproduction by NK cells during acute inflammation and regulates the expansion and function of IFN-γ-secreting Th 1 CD4+ T cells during Ag-specific cellular immunity . IL-12 has proven to be a key regulatory cytokine in the host response against infection with parasites, viruses, and bacteria and in the rejection of tumor cells. As described above, IL-12 also mediates destructive inflammatory effects in endotoxic shock and may contribute to the pathogenesis of autoimmune diseases such as lupus nephritis and asthma.It can protect asthma patients from outbreak through controlling the airway hyperrreactivity.Consequently, the ability of the host to self-regulate IL- 12 bioactivity may be critical in the pathogenesis of a variety of infectious and/or inflammatory diseases. Homodimeric p40 competes with heterodimer for binding to the high affinity IL-12R and inhibits IL-12 bioactivity in vitro,presenting with Th2 domination. It also has played an important role in infectious and autoimmune diseases such as rheumatoid arthritis ,system lupus erthyma and so on.We hypothesized that the production of p40 homodimers may represent such a mechanism.MCP-1 is a member of the C-C chemokine family,which has been shown to play a major role in the migration of monocytes and lymocytes to an inflammatory focus,accompanied by activating monocytes/macrophages and memory T lymphocytes selectively.Recent studies reported that MCP-1 can regulate immunity, respair injury and maintain the environment stabilization of human body in the host defense.Except for that ,it also influence the polarization of TH0. MCP-1 can orientate the differentiation from Th0 to Th2 through inducing IL-4 and I1-10 and depressing IFN-γand IL-12 by binding to the high affinity CCR2 on dentric cell. But overexpression of chemokines can causes injury on tissues,inflammatory chronicity. Studies presently reported that MCP-1 has play a critical role in inflammatory bowel disease ,central and genitourinary infect disease,idiopathic pulmonary fibrosis and so on.People newly report that MP are capable of invading target cells and survive intracellularly for a long-term. IL-12 is a critical cytokine in immunity defense of intracellular pathogeny.Researches from abroad and internal report that IL-18 contributes a lot in the pathogenesis of MP.IL-12 can be assistant to the expression of IL-18 receptor on T cell.and so can IL-18 elevate the expression of IL-12 receptor on APC cell. Both of them promote the production of IFN-γand Th1 cell immunity. As people internal suggest the function of Th2 cell immunity is central in MP infection,we speculate whether IL-12p40 has play a role in its pathogenesis,and it is concerned with the imbalance of Th1/Th2.However,at present there is few reports about production and significance of p40 monomer and homodimer in children with MP.In this study,we observed the level of IL-12p40 in patients with MP ,which was the second problem discussed here.Another thing,we found that monocytes elevated in peripheral blood of MP patients and histopathology showed a great deal of lymphocytes,especially CD4+ T lymphocytes invading around brochia and blood vessels at first and then macrophages immerging into bronchus in MP infected animal models.The fact described above suggests monocytes/macrophages may involve the pathogenesis of MR However the role of MCP-1 in MP infection is still not clear. Whether the monocytes immerging in the MP inflammation was induced by MCP-1 or not and extrapulmonary symptom was associated with MCP-1.That was the other aim of the study discussed here.In this study we choose 40 patients infected with MP as observation group,including groups Pn1 and Pn2,which were not treated with hormone and except other pathogen mixed infection.Simultaneity 20 pneumonia patients and 20 healthy children were randomly choosed as control group. Serum levels of IL-12p40 and MCP-1 of three groups were detected by double-sandwich mAb ELISA.The Newman-Keuls test was used to analyze differences between trhee groups in cytokines production and T test was carried between group Pn1 and Pn2 which resectively consist of mild patients and severity ones.The statistic results show that the level of MCP-1 in observation group was much higher than the others and the level of group Pn1 was higher than that of Pn2 while IL-12p40 showed no distinct difference. These results suggest MCP-1 involve in the pathogenesis of MP, associated with the state of illness and L-12p40 might not contribute critically to the pathogenesis of MP infection. We speculate MCP-1 may involve in activating monocytes/macrophages and T lymphocyte and the imbanlance of Th1/Th2 in the infection of MP,which need our further work. Moderate expression of MCP-1 is good to control inflammation ,while overexpression can injure organism . The role of MCP-1 in MP infection may be assistant to help us find a new way in treating immune injure.
Keywords/Search Tags:Interleukin-12p40
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