Immune response after syngeneic and allogeneic blood cell transplantation.
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Biomedical subjects
Publications and source records attributed to I Grzelak.
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In the period from January 1992 to May 1997 we performed 20 procedures of percutaneous transjugular intrahepatic porto-systemic shunt (TIPS) in the patients with liver cirrhosis and recurrent variceal bleedings. This group consisted of 10 male and 10 female patients, their age ranging from 17 to 68 years (average 52). The etiology of cirrhosis was alcoholic in 8 cases, postinflammatory in 6, primary biliary in 4 and autoimmunological in 2 cases. According to Child-Pugh classification 4 patients represented group A, 10-group B and 6-group C. Each of these patient was admitted to our Department after recurrent bleeding, resistant to typical treatment: vasopressin infusion, balloon tamponade and endoscopic sclerotherapy. In 3 cases TIPS was performed in candidates for orthotopic liver transplantation.
UNLABELLED: This study is aimed at the clinical and morphological criteria of estimation of the liver harvested for transplantation. In the period from January 1996 to May 1997 our team obtained 26 livers at the multi-organ harvesting. Most of the donors were young people after the trauma of central nervous system. The liver was harvested according to the principles of Starzl's fast method with the successive preparation on the "cold table". The donor's clinical status was estimated, as well as appearance, density and colour of the organ, quality of perfusion with UW solution In 23 cases the histological examination of the harvested organ allowed to estimate the degree of steatosis, hepatocyte necrosis, vacuolar degeneration and other abnormalities. In 3 cases the graft was estimated only by means of macroscopic examination. RESULTS: As a result of clinical and histological findings 8 organs were considered as unsuitable for transplantation. In one case the histological findings were the contraindication despite the satisfactory macroscopic appearance of the organ 15 organs were successfully transplanted, proving the conformity of clinical and histological criteria. In 4 livers (15%) the abnormalities of arterial supply were found. CONCLUSIONS: Clinical and pathomorphological estimation of the harvested liver is adequate to it's suitability for transplantation, advisable for the centres initiating the liver transplantation program. Detailed analysis of the donor's clinical status and laboratory data and competent macroscopic estimation of the harvested liver allow the experienced surgeon to resign from the routine histological verification, which might be necessary in doubtful cases only.
The exact changes in cytokine production and clinical implications of the increased cytokine levels following operative trauma remain unclear. In this study, systemic production of a spectrum of cytokines, including IL1 alpha, IL1 beta, IL6, IL8, IL10, and IFN gamma, was examined in patients undergoing minor elective operative trauma. The levels of IL1 receptor antagonist (ra) and IL6 soluble receptor (sR) were also determined. Although there were no changes in IL1 alpha and IL1 beta plasma levels during the entire observation period, there was a significant rise in IL1 ra level in all patients between postoperative day 1 and postoperative day 14. A significant increase in the IL6 plasma level was seen on days 1, 3, and 7 after surgery and an increase in the IL6 sR level was observed on postoperative days 10 and 14. Interestingly, the IL8 plasma values had risen significantly on days 1 and 3 following the operation. In some patients, an elevation in IL10 plasma level was noted on days 1 and 3 postsurgery. Results demonstrated that even a minor surgical procedure such as cholecystectomy with uneventful wound healing was followed by an appearance in the blood circulation of significant levels of cytokines between day 1 and day 14 after surgery. These observations point to the necessity of searching for methods of down-regulating the systemic cytokine effects after surgical trauma for the routine postoperative management.
Blood transfusions (BT) should be considered as transplantation of blood elements. They evoke various alterations in the immune responsiveness of blood recipients, contributing to an increased risk of infection and cancer recurrence. The exact mechanism by which blood transfusions induce a state of reduced immune responsiveness remains unclear. Relatively little is also known about immune changes occurring in lymphoid compartments other than blood following blood transfusions. In the present study, the effect of syngeneic and allogeneic blood transfusions on hemopoiesis and immune responsiveness was examined in a rat model. Transfusions of both syngeneic and allogeneic blood caused an increase in the bone marrow myeloid and lymphoid lineage cell compartments as well as a rise in the percentage of OX7+ stem cells in bone marrow. It was followed by a release of OX7+ stem cells into blood circulation, higher in the case of rats transfused with syngeneic blood. The changes in hemopoiesis were accompanied by a diminished responsiveness of blood, spleen and bone marrow lymphocytes to mitogens in both groups of rats. Data point to early changes in distribution and reactivity of bone marrow and lymphoid cells following blood transfusion.
In December 1994 an orthotopic liver transplantation was performed in a 46-year old female patient with liver failure due to primary biliary cirrhosis. The patient was discharged on the 31-st postoperative day. The graft was obtained at the multi-organ harvesting. The results of the donor's biochemical tests and the histological estimation of the graft tissue allowed to prognose a successful postoperative course.
The authors present 225 patients with various forms of portal system venous thrombosis (PSVT), of various origin and etiology. The largest group (120 patients) were the young people suffering from portal hypertension due to pre-hepatic venous obstruction of uncertain etiology, lasting since childhood. The next group consisted of 75 patients with liver cirrhosis coexisting with PSVT. In other cases PSVT was diagnosed as coincident with: Budd-Chiari Syndrome (8 cases), liver tumors (9 cases), chronic pancreatitis (3 cases) and polycythaemia (2 cases). In 3 cases PSCT developed postoperatively and in 5 cases after oral contraceptives. Diagnosis of coexisting PSVT deteriorates the prognosis in liver cirrhosis. The overall mortality was 16%. The course of the disease depends on extensiveness and dynamism of thrombosis, but consequently leads to the development of portal hypertension. The most effective diagnostic procedures are: CT and USG with Doppler flowmetry. Bleeding esophageal varices require either sclerotherapy or surgical treatment--decompressive shunts or "non-shunt" procedures. In the cases of recent thrombosis, without bleeding varices, thrombolytic therapy appears to be effective.
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Immune proteins and cytokine concentrations and activity were measured in skin tissue fluid-lymph and blood serum of patients with lower leg filarial lymphedema. High levels of lymph gamma-globulins, alpha-1-acid glycoprotein and IgG lymph/serum ratio were found. Lymph from filarial patients had an elevated lymph stimulatory effect on blood mononuclear cell culture with phytohemagglutinin. There was also a high concentration and activity of IL-1 beta but gamma-interferon was not detected. The deranged pattern of immune proteins and high activity of IL-1 suggest persistence of an ongoing local inflammatory process despite the absence of overt dermatitis. The high tissue-lymph IL-1 concentration and activity may signify a cytokine network promoting keratinocyte and fibroblast proliferation commonly seen on skin histology in patients with filariasis.
The influence of moderate operative trauma on lymphocyte responsiveness to phytohemagglutin (PHA) and in autologous mixed lymphocyte response (AMLR) was studied. Furthermore, production of interleukin 2 (IL2) and immunomodulatory effect of exogenous IL2 on lymphocyte reactivity after surgery were examined. The responsiveness to PHA declined on day 1 (p less than 0.05) and the level of AMLR was found decreased on days 1 (p less than 0.05), 3 (p less than 0.02) and 5 (p less than 0.03) after surgery. Production of IL2 significantly decreased on day 1, 3 and 5 (p less than 0.05) after operation. Supplementation of PHA and AMLR cultures with exogenous IL2 restored the attenuated postoperative responsiveness to the levels observed preoperatively. This observation may justify IL2 therapy in surgical patients with high risk of uncontrollable postoperative infections.
Cell-mediated immune responsiveness was evaluated in 8 patients with dilated cardiomyopathy (CDM). The percentage of blood OKM1 (monocytes), OKT3 (T-cells), OKT4 (helper cells), OKT8 (suppressor cells) and Leu7 (NK) positive cells remained within the normal range whereas the percentage of Leu11 (NK) and OKIa1 (Ia determinant) positive cells was found to be decreased. The natural killer (NK) cell cytotoxicity was significantly lowered. The ConA-suppressor cell activity was seen to be enhanced while the responsiveness of lymphocytes to ConA was diminished. Thus, no consistent numerical changes in lymphocyte subsets were observed in patients with CDM. Some functional deficiencies were, however, detected, and it is possible that these may play a role in the pathogenesis of CDM.
Lymph stasis in the extremities caused by interruption of lymphatics or insufficient lymph propulsion is often complicated by recurrent skin infections. To shed further light on this subject, we studied the phenotypical and functional characteristics of cells in peripheral lymph and skin of patients with obstructive lymphedema. Compared with controls, patients with secondary lymphedema displayed a high concentration of lymphocytes and erythrocytes in peripheral lymph, sometimes increased numbers of B cells, increased density of Langerhans cells in the epidermis and occasionally in the skin papillary layer, strong expression of class II antigens on skin endothelial cells and mononuclear infiltration around blood vessels, and margination of granulocytes in skin blood vessels. Reactivity of lymph cells to mitogens was augmented. Taken together these findings indicate that ongoing chronic inflammatory processes persist in skin with lymph stasis, and, moreover, with impaired lymphocyte and Langerhans cell trafficking from skin to regional lymph nodes and inefficient clearance of foreign antigens, these lymphedematous limbs become susceptible to infection.
The effects of 3 h lasting local hyperthermia on immune cell traffic through the normal human skin to afferent lymphatics, cell phenotypes, responsiveness, and stimulatory properties were studied in eight men. Cells were harvested from lymph drained from foot skin. Heating the skin in a water bath of 44 degrees C (skin temperature 2 mm under the surface 39 degrees C) evoked an augmented traffic of mononuclear cells to lymph with preponderance of large, macrophage-like, Ia-positive cells, among them Langerhans cells. Lymphocytes obtained from the heated skin lymph revealed in cultured increased spontaneous blastic transformation rate, augmented responsiveness to phytohemagglutinin (PHA), and enhanced PHA-presenting properties to autologous peripheral blood mononuclear (PBM) cells. An increased stimulatory activity on allogeneic mixed lymphocyte reaction (MLR) was also observed. Lymph from heated skin augmented the PBM responsiveness to PHA and showed increased interleukin-1-like activity. Local heating of the skin is a potent signal initiating augmented traffic, and enhanced responsiveness and stimulatory activity of "passenger" immune cells. Their rapid nonspecific activation makes them indiscriminately active against a wide range of antigens before the specific response is developed.
The in vitro interleukin-1 (IL-1) and interleukin-2 (IL-2) production and IL-2 receptor (IL-2-R) expression by peripheral blood mononuclear (PBM) cells were examined in patients undergoing elective cholecystectomy. The IL-1 production by monocytes stimulated with a lipopolysaccharide (LPS) did not change on day +1 but increased by 57.5% on day +3 (p less than 0.05) after surgery, and was normalized on days +5 and +7. The IL-1 production by PBM cells stimulated by LPS increased by 97.6% on day +1 (p less than 0.05) and 109.5% on day +3 (p less than 0.05) after surgery, and became normalized on days +5 and +7. The IL-2 level in PBM cell supernatants stimulated with phytohemagglutinin (PHA) decreased by 45.2% on day +1 (p less than 0.05), 33.3% on day +3 (p less than 0.05), 32.3% on day +5 (p less than 0.05) and returned to the preoperative values on day +7. The IL-2-R expression on PHA-stimulated lymphocytes increased from 60.4 +/- 4.8% preoperatively to 67.2 +/- 1.9% on day +1 (p less than 0.05) but was again within the preoperative values on days +3, +5 and +7. In order to detect the described changes, stimulation with PHA had to be used. This indicates that simple surgical trauma produces subthreshold activation of blood immune cells. The cells enter the 'response alert' stage which can be measured after stimulation with lectins.(ABSTRACT TRUNCATED AT 250 WORDS)
Cell-mediated immune responsiveness was evaluated in 8 patients with dilated cardiomyopathy (CDM). The percentage of blood OKM1 (monocytes), OKT3 (T-cells), OKT4 (helper cells), OKT8 (suppressor cells) and Leu7 (NK) positive cells remained within the normal range whereas the percentage of Leu11 (NK) and OKIa1 (Ia determinant) positive cells was found decreased. The NK cell cytotoxicity was significantly lowered. The ConA-suppressor cell activity was found increased while the responsiveness of lymphocytes to ConA decreased. Taken together, no consistent numerical changes in lymphocyte subsets were observed in patients with CDM, however, some functional deficiencies which may play a role in the pathogenesis of CDM were detected.
The effect of surgery on peripheral blood mononuclear cell responsiveness to mitogens and suppressor cell (SC) activity assessed in a concanavalin A (ConA) assay were studied in patients with stage 0 and stage III-IV cancer. Patients were exposed to a similar surgical trauma the same type of anaesthesia, and to no pre- and early postoperative radio- or chemotherapy. A more pronounced postoperative decrease in the lymphocyte count, responsiveness to phytohemagglutinin (PHA) and ConA, and in the SC activity was found in the nonadvanced than advanced cancer group. These findings point to an impaired mobilization and distribution capacity of circulating lymphocytes in patients with advanced neoplastic disease.
Interleukin 1 was isolated from human lymph drained from normal skin. The lymph was separated by gel filtration chromatography on Spherogel TSK SW 2000 column. IL-1 activity was found in three fractions: greater than 70 kD, 13-16 kD and 5-5.5 kD. Additionally a slight IL-1 activity was found in the 36-40 kD fraction. When exogenous IL-1 was added to the lymph inhibitory activity was detected in fractions: greater than 70 kD, 22-30 kD and 5.5-8 kD.
Lymph derived from human skin contains lymphocytes which have a high rate of spontaneous blastic transformation in culture and are highly responsive to lectins. This phenomenon suggests that either a subpopulation of highly responsive lymphocytes is extravasated into skin, or skin tissue fluid and lymph contain humoral factors co-stimulating lymphocytes upon contact with tissue antigens. We sought to determine whether human prenodal lymph drained from normal leg skin possesses lymphokine activity. Significant augmentation of lectin induced thymocyte and autologous blood lymphocyte proliferation was produced by lymph. The augmenting activity was abrogated by incubation of lymph with anti-IL-1 antiserum. Supernatant from cultured lymph cells (lymphocytes, Langerhans cells) did not augment either thymocyte or autologous blood lymphocyte proliferation. No interleukin 2 activity was found in lymph. The data indicate that skin lymph possesses epidermal cell thymocyte activating factor/interleukin (ETAF/IL) 1-like activity which is not found in serum and that the main source of the putative lymphokine is epidermal and not migrating lymph mononuclear cells.