Study On Status And Regulation Of Cellular Immunity In Obstructive Jaundice

Patients with obstructive jaundice are susceptible to systemic inflammatory response syndrome(SIRS),even sepsis and multiple organ dysfunction syndrome(MODS) perioperatively. Mortality as high as 15₂0% still by new data. It has been proposed that obstructive jaundice resulted in impairment of immune function, cellular immunity especially. Such as: Decreased elimination of endotoxin and bacteria by Kupffer cells; Impaired allergic reaction on cutis in patients with obstructive jaundice; Decreased concentration of interleukin 2(IL-2), Impaired cell-mediated immunity.Although people has done a lot of work on the immune status in obstructive jaundice, the mechanisms of impaired immune function are not folly understood yet. Now, there are two points of view primarily : (1) cholestasis contributes to hepatocellular injure and immunecellular injure directly;(2) immune suppress factors exist in blood in patients with obstructive jaundice, proposed as bile salts,bilirubin,α-globulin and endotoxin, but, the mechanisms of they induced immune dysfunction in obstructive jaundice remain incompletely understood.Recently, it has been proposed that Th₁/Th₂ cell-balance has a important role in immunity. Helping T cell (Th) is divided into two parts on two kinds of cytokines excreted by CD₄⁺ T cell,—— Th₁ and Th₂ cell. Th₁ cell can excrete IL-2,ILN-r et al, it's in charge of cellular immunity primarily; Th₂ cell can excrete IL-10,IL-6,IL-4 et al, it's mostly in charge of humour immunity . Lots of data show that the production of IL-2 excreted by T cell is decreased significantly, and part test show that IL-10,IL-6 increased distinctly in obstructive jaundice early, these suggest disturbance of Th₁/Th₂ cell-balance . IL-2,enable to promote reproduction of active T lymphocyte, improve activity of natural killer(NK) cell ,play a important role in cellular immunity; IL-10,enable to suppress the production of IL-2 and the reproduction of active T lymphocyte, to induce pro-T cell transferring to Th₂ cell, is a important suppress-inflammatory cytokines; Prostaglandin E₂(PG E₂) is a important mediators in inflammation and immunity, enable to suppress T cell production of IL-2; It can mediate the expression of IL-10 in recent studies also. Now, lots of observations show PGE₂ production was increased in obstructive jaundice. we know Th₁/Th₂ cell-balance depending on action of many cytokines and factors has a central role in immune regulation, out of these, PGE₂ and IL-10,IL-2 are important representatives. But, study on relativity of PGE₂ and IL-10,IL-2 following obstructive jaundice has not been reported now.The present experiment measured the serum PGE₂ and the IL-10, IL-2 expression levels of blood lymphocyte in rats with experimental obstructive jaundice in series and their correlationto study the mechanism of immune dysfunction in patients with obstructive jaundice. With the study of animal clinic we try to provide theoretical basis for researching new method of treatment.The experiment consist of 3 parts:Part 1Study on relativity of prostaglandin E₂ and IL-10,IL-2 following obstructive jaundice.1. Objectivewe Study the serum PG E₂ and the IL-10,IL-2 expression levels of blood lymphocyte in rats with experimental obstructive jaundice in series and their correlation, try to provide theoretical basis for researching new method of treatment.2. Materials and Methods (1) Materials and Groupsâ‘ .Seventy SD rats(balance of male and female, weight: 180-240 g) were randomly divided into Sham group(n=10),bile-duct ligation(BDL) 1 Week(n=20),BDL 2 W(n=20),BDL3 W(n=20). â‘¡.PE₂,IL-10,IL-2 test boxes.(2) Methods â‘ .Experimental obstructive jaundice(BDL) was induced by doubleligation and clipping of the bile duct that underwent BDL for 1,2,3weeks. No BDL in sham groups. â‘¡. Collecting PGE₂ from vein blood in abdomen cavity, test it byRadioimmunoassay. â‘¢. Isolated lymphocyte from vein blood in abdomen cavity, producingIL-10,IL-2, test by ELISA. â‘£. BDL rats for 1,2,3W were died and pathological change of thymuswere detected. ⑤.The treatment of statistics: all data were expressed by (X|-)±S. Thesignificance test of diversity in classifications by t analysis . 3. Results(1) The pathological change of thymus:The weight of thymus and the amount of lymphocytes were decreased significantly in 3 week in BDL rats. Table 1. (2) The changes of serum PGE₂ and IL-10,IL-2 expression levels of blood lymphocyte in BDL rats:The serum PG E₂ and the IL-10 expression levels of blood lymphocyte in rats significantly increased at 1 and 2W after BDL, P < 0.05, and keep their levels at 3W. A positive correlation was found between PG E₂ and IL-10 levels, r=0.878,P < 0.01; IL-2 level significantly decreased at 3W in rats after BDL, P < 0.05, and relativity between PG E₂ and IL-2 levels is significant, r = -0.645, P < 0.05. Table 2.4. ConclusionsObstructive jaundice results in imbalance of immune function due to the impaired cellular immunity, and probably, it related to the increased serum PG E₂ after cholestasia. This provides theoretical basis for researching new method of treatment, indothemycin suppressing the production of PGE₂, may be effective in increasing immune function and reducing postoperative complications in patients with Obstructive jaundice. Part 2Effects of indothemycin on production of IL-10,IL-2 in patients with Obstructive jaundice1. Objectivewe Study the serum PG E₂ and the IL-10,IL-2 expression levels of peripheral blood lymphocyte in patients with obstructive jaundice , and action of indothemycin on them , try to provide theoretical basis for researching new method of treatment.2. Clinic data and Methods (1) Clinic data16 patients with Obstructive jaundice, male =10 cases, female = 6cases, mean age = 52.4; 10 healthy adults as sham. (2) Methodsâ‘ . We treated the patients with indothemycin for 7 days (25mg, 3/day, take orally) in treated groups.â‘¡. We collected peripheral blood from patients apartly on time( before drug given, and 7 days after drug given), Collecting PGE₂ and test it by Radioimmunoassay, Isolating lymphocyte from peripheral vein blood , producing IL-10,IL-2 and test it by ELISA.â‘¢. The treatment of statistics: all data were expressed by (X|-)± S. The significance test of diversity in classifications by t analysis .3. Results (1) Before drug givenComparing to sham, The serum PG E₂ and the IL-10 expression levels of blood lymphocyte in patients with Obstructive jaundice significantly increased and the IL-2 expression level significantly decreased, P<0.01。(2) After indothemycin given for 7 daysComparing to pre-drug given, The serum PG E₂ and the IL-10 expression levels of blood lymphocyte significantly decreased and the IL-2 expression level significantly increased , P < 0.05; And, significant correlation were found between the serum PG E₂ and the IL-10,IL-2 expression levels of blood lymphocyte (r_IL10= 0.868, P < 0.05, r_IL-2 = -0.586, P < 0.05. Table 3 4. ConclutionFrom our results, we concluded that immune dysfunction in patients with obstructive jaundice may be the reason for high susceptibility to infection and indothemycin might become a valuable drug for improving immune function and decreasing susceptibility to infection.Part 3 Perioperative Action of Angelica on cellular immunity in Patients with Obstructive Jaundice1. ObjectiveIn order to study the action of angelica on immune function in patients with Obstructive jaundice, we measured the activity of IL-2 and expression of receptors IL-2(IL-2R) in blood lymphocytes , helping us to search new drugs for reducing postoperative complications in patients with Obstructive jaundice.2. Clinic data and Methods (1) Clinic data14 patients with Obstructive jaundice, male =10 cases, female = 4 cases,mean age = 48; 10 healthy adults as sham. (2) Methods â‘ . We treated the patients with angelica perioperatively(8mg/kg/d),total 14days, 10 days before operation and 4 days after operation intreated groups. â‘¡. We collected peripheral blood from patients apartly in time( beforedrug given, 10days before operation, 4 days after operation), IL-10,IL-2R test by ELISA. â‘¢. The treatment of statistics: all data were expressed by (X|-)± S. Thesignificance test of diversity in classifications by t analysis .3. Results (1) The results show that the activity of IL-2 and the expression of IL-2R significantly decreased in patients with obstructive jaundice . P< 0.01.(2) Perioperatively using angelica could increase the activity of IL-2 and the expression of IL-2R significantly. Continuous application of the drug after operation could also reduce the operation-mediated immune suppression effectively. P<0.01. Table 44. ConclutionThe results suggest that perioperatively using angelica is practicable in increasing immune function of patients with obstructive jaundice, angelica might become a valuable drug for decreasing susceptibility to infection in patients with obstructive jaundice. Summary1. Our study show that: Obstructive jaundice results in imbalance of immune function due to the impaired cellular immunity, and probably, it related to the increased serum PG E₂ after cholestasia. This provides theoretical basis for researching new method of treatment, indothemycin suppressing the production of PGE₂ , may be effective in increasing immune function and reducing postoperative complications in patients with Obstructive jaundice.2. From our results, we concluded that immune dysfunction in patients with obstructive jaundice may be the reason for high susceptibility to infection and indothemycin might become a valuable drug for improving immune function and decreasing susceptibility to infection. But, the actions of prostaglandin, which include lots of contents, are complex physiologically and pathologically. For example, prostaglandin I₂(PG I₂) play a important role in maintaining the normal renal blood flow and glomerular filtration in patients with obstructive jaundice. We must study deeply the changes and reciprocities of important immune and inflammatory factors with obstructive jaundice.3. The results suggest that perioperatively using angelica is practicable in increasing immune function of patients with obstructive jaundice, angelica might become a valuable drug for decreasing susceptibility to infection in patients with obstructive jaundice.