Proinflammatory cytokine, cytokine reseptor and chemokine responses in cystic echinococcosis

Background: Cystic echinococcosis (CE) caused by the larval stage of Echinococcus granulosus (E. granulosus) which is widespread all around the world and Turkey, is a very important parasitic disease regarding both the public health and the economy. The clinical forms of the disease are various and severity of the disease is changeble that point at different immune response patterns to the disease. Immunological parameters, especially in the last decade, are investigated to determine the development, clinical course and outcome of CE and the different immune responses. The new perspectives in this area, originate from the studies where Th1 and Th2 immune responses in CE coexist. For this reason, it is of great importance to investigate the roles of spesific cytokines, cytokine receptors and chemokines that function in these immune responses in CE.Aim: In this study, our objective was to investigate IFN gamma, interleukin IL4, IL12(p40), IL13, the solubl IL2 cytokine receptor (sIL2Ralfa), proinflammatory cytokine IL1beta and chemokine IL8, their relationship with each other, their roles in the development, clinical course and outcome of the disease, to evaluate the IgG antibody responses in the cured CE patients after surgery and in the progressive CE patients and to determine the different immune responses in different CE patients in Turkey .Material and Methods: IFN gamma, IL4, IL12(p40), IL1beta, sIL2Ralfa, IL13 synthesis of the peripheral blood mononuclear cells (PBMC) from 10 cured CE patients, 19 progressive CE patients and 13 healthy volunteers and IL1beta, sIL2Ralfa, IL8 levels in the sera of them were investigated by using commercial ELISA sets and kit. The IgG antibody responses in the sera of all the patienst and volunteers were determined by in house ELISA. For statistical analysis, SPSS 16.0 software programme was used.Results: None of the cured CE patients and the healthy volunteers were positive for spesific IgG while 74% of the progressive CE patients exhibited spesific IgG responses. IFN gamma (Th1 cytokine) production of PBMCs from cured CE patients was significantly higher than the production of PBMCs of both the progressive CE patients and healthy volunteers (p<0,0167). IL4 (Th2 cytokine) was detected significantly higher in supernatants of PBMC cultures from progressive CE patients than the concentrations detected in the supernatants from healthy volunteers (p=0,03). When the progressive CE patients divided into two groups with liver or lung cysts, the ones with liver cysts had significantly higher IL4 concentrations (p=0,029). In the progressive CE patients, significant positive correlation was found between IFN gamma and IL4 responses (for 25 ? g/ml and 10 ? g/ml antigen concentrations r=0,520 and r=0,487 respectively, p<0,05). In addition to this, regarding all the people in the study, significant medium positive correlation was found between IL4 responses of PBMCs stimulated with 25 ? g/ml, 10 ? g/ml and 5 ? g/ml antigen concentrations and IgG responses in sera (r=0,383, r=0,317 and r=0,419 respectively, p ? 0,05). IL12(p40) production of PBMCs was higher in cured CE patients than healthy volunteers (p=0,015). Progressive CE patients had significantly higher levels of IL2sRalfa in the supernatants from PBMCs compared to control group (p ? 0,05). IL13 production of PBMCs of both the cured and progressive patients was higher than the healthy volunteers (p>0,05). The levels of IL1beta, IL2sRalfa ve IL8 levels in sera did not differ significantly between groups (p> 0,05).Conclusion: Especially in the clinical follow up of the CE patients cured with drug or surgery, it is more useful to use IgG ELISA test with different kinds of tests searching different antibody responses such as IgG4 or IgE. The coexistence of IFN gamma and IL4 in both the cured and progressive patients, the higher levels of these cytokines in patients? PBMCs than the levels in healthy volunteers? PBMCs and also the significant positive correlation found between IFN gamma and IL4 responses in the progressive CE patients, point at that cyst fluid has different antigenic epitops and so, in CE Th1 and Th2 cells are activated together. The high IFN gamma production in the cured patients after surgery implies Th1 cell activation in protective immunity. For this reason, levels of IFN gamma in CE patients before and after surgical therapy may be useful for the clinical follow up after the surgery. Besides, because the high concentrations of IL4 was detected in supernatants from patients? PBMCs and the significant positive correlation was found between IL4 and IgG responses, IL4 may be a useful marker to determine the progression in CE. The high levels of IL12(p40) detected in cured patients indicate the association of this cytokine with the surgical treatment of CE and the critical role of IL12 in getting cured from the disease after surgery. Consequently, IL12 may prove useful with IFN gamma and spesific antibody responses in the clinical follow up of patients after surgery. The results of this study are expected to be useful for the further researches related to the immunity in CE, as they support the existing studies or contribute the new ones.