Effects Of Bladder Dendritic Cell And Urine IL-2 On The Different Intravesical Instillation

Background and objectiveBladder cancer(Bca) is the most common tumor of the genitourinary tract.The most important clinical character of Bca is the high incidence rate,high recurrence rate,and low malignancy.Intravesical instillation is an effective device for prophylaxis of the recurrence of bladder cancer . Orthodox intravesical instillation agents include BCG(Bacillus Camette-Guerin),Mitomycin C,Thiotepa,Doxorubicin and so on,and BCG is the most available and used extensively in those orthodox agents.With the development of medical technology,many new intravesical instillation agents are adopted in the clinic,such as Pirarubicin,Combination of Pirarubicin and BCG; Combination of IL-2 and BCG; Combination of Pirarubicin and Mitomycin C; Pharmorubicin; Combination of BCG-CWS and IL-2,HCPT,α-interferon and so on.The curative effect of those new intravesical instillation agents come from clinical observation,but each of these new agents have not received unanimous affirmation.In these new agents,there are many documents that report that the curative effect of Combination of IL-2 and BCG is better than BCG single,but how the combination of IL-2 and BCG can improve curative effect and the mechanism about prophylaxis of recurrence of bladder cancer are reported very rarely (I have not found any correlated reports in our country).The objectives of this study are to contrast and analyse the effects of three different intravesical instillation agents: Combination of IL-2 and BCG,BCG alone and mitomycin-c,for bladder dendritic cell(DC) and urine IL-2 on female wistar rats,and to investigate the correlative immune mechanism of combined instillation of BCG and IL-2 in the prophylaxis of recurrence of bladder cancer.We will offer supporting theory for the superiority of combination of IL-2 and BCG,at same time,we can try to find a new thinking to search some theory target to judge curative effect of different intravesical instillation agents.DC(dendritic cell)was found by Steinman,an American scholar,in 1973.DC,as a superior antigen presenting cell (APCs),it's function is the most powerful in the body.To distinguish other antigen presenting cells (APCs),the most characteristic of DCs is to irritate naive T cell proliferation and supply important adhesion and costimulatory molecules to lymphocytes.Immature DCs are efficient antigen-capturing cells,inflammatory factors,TOLL-like receptor ligands such as bacterial components and BCG,CD40L,TFN-αaffect their differentiation into mature DC.Mature DC have activation and maintenance of CTL,high expression of major histocompatibility complex (MHC) molecules,costimulatory molecules such as CD83,CD86,CD54,CD40,and secrete a lot of IL-2.So DC play a important role in the immune response.There are many studies on the relationship between DC and bladder tumor.The quantity of DC in bladder tissue can reflect grade,stage and prognosis.The inhibitory effect of cancer by IL-2 has been studied in many articles at present.First,IL-2 can irritate T cell proliferation,differentiation,and maturity.Second,IL-2 can induce an expression of IL-2R and excite an organism to excrete cytokine such as TNF,IFN-γ.Last,IL-2 can irritate B cell,NK,and macrophage activation.All of these effects can improve organism immune function.Materials and Methods44 female wistar rats were divided into control groups,combination of IL-2 and BCG group,BCG alone group and mitomycin group.The following was carried out on each group: periodic intravesical instillation,removal of the bladder and collection of urine after the animal was put to death.Immunohistochemistry was used to examine the dendritic cell and ELISA to examine the density of urine IL-2,and the change of DC and urine IL-2 observed.Result1,The average amount of DC : combination of IL-2 and BCG group (28.4±8.0CDS/HPF),BCG alone group(16.6±5.9CDS/HPF),mitomycin group (4±2.3CDS /HPF),control group(4.8±3.4CDS/HPF).2,the density of urine IL-2:combination of IL-2 and BCG group(87.5±30.4 ng/L),BCG alone group(58.7±20 ng/L) and mitomycin group(35.9±9.6ng/L),control group (35.7±11.3 ng/L).3,intravesical instillation of a combination of IL-2 and BCG improve not only local immunity,but also general immune state. 4,intravesical instillation of a combination of IL-2 and BCG would help organism maintain immune state for a long time.Conclusion1,intravesical instillation of a combination of IL-2 and BCG would improve the immunological reaction and synergistic effect.2,intravesical instillation of a combination of IL-2 and BCG would effectually induce maturity of DCs,improve migratory capability of DCs and stimulate the T cells to secrete more IL-2.3,To provide theory support for the superiority of combination of IL-2 and BCG.