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The effect of steroids on the circulating lymphocyte population--VI. Studies of the thoracic duct T- and B-lymphocyte populations after neonatal thymectomy and prednisolone treatment. An immunofluorescence study in the rat.

The corticosteroid effect on circulating lymphocytes in a steroid-sensitive species (rat) was studied by immunofluorescence. Both normal and neonatally thymectomized animals were injected with a high dose of prednisolone. T- and B-lymphocytes as well as T-lymphocyte subsets were analyzed in thoracic duct lymph during the involution phase (3 h after injection) and the restitution phase (17 h after injection) using conventional and monoclonal antisera. Neonatal thymectomy significantly reduced the number of circulating T-helper and T-non helper cells. In the involution phase, after a corticosteroid injection, there was a 64% reduction of lymph cell content in normal rats, affecting both T- and B-lymphocytes. Thymectomized animals showed an even more pronounced disappearance of cells. Counted in percentage, more B- than T-lymphocytes disappeared from the circulation. The T-non helper cells disappeared to a greater extent than the T-helper cells did. Cells with Ia-antigen showed about the same values as the B-lymphocytes. During the restitution phase all cells types were restored to normal levels. It seems that a high prednisolone dose has a more pronounced effect on the circulation of B- than of T-lymphocytes, and the T-non helper cells are probably more sensitive than the T-helper subpopulation. These data support the hypothesis that a major corticosteroid effect is a trapping and redistribution of circulating lymphocytes, more pronounced for certain cell types.

Animals↗

Lymph distribution of different non-steroidal anti-inflammatory drugs assessed by microsurgical cannulation of the thoracic duct in rat.

The motility of lymphatic vessels is regulated by arachidonate metabolites and, therefore, can be altered by cyclo-oxygenase blockers such as non-steroidal anti-inflammatory drugs (NSAIDs). In order to investigate the lymphotropic properties of different NSAIDs, pharmacokinetics in plasma and lymph following intragastric administration of three model compounds, namely racemic ibuprofen, tenoxicam and nabumetone, were investigated in rats. Microsurgical cannulation of the thoracic duct allowed cumulative sampling of lymph fluid up to 48 hrs (n = 16). Pharmacokinetic parameters in plasma were determined in a control group (n = 12). Concentrations of R-, S-ibuprofen, tenoxicam, nabumetone and the metabolites OH-ibuprofen, COOH-ibuprofen and 6-methoxy-2-naphthyl-acetic acid (6MNA, metabolite of nabumetone) were monitored in lymph and plasma by HPLC. To quantify the lymphotropic properties of the investigated compounds, a "lymphatic clearance" was defined by dividing the amount recovered in lymph fluid by the corresponding area under the plasma concentration-time curve (AUCP). The "lymphatic clearance" substantially differed between the investigated compounds (mean +/- SD: R-ibuprofen 6.71 +/- 3.15 microliters/min, S-ibuprofen 3.24 +/- 1.20 microliters/min, tenoxicam 8.74 +/- 8.11 microliters/min, nabumetone 46.05 +/- 26.08 microliters/min and 6MNA 6.32 +/- 2.96 microliters/min). The overall recovery of the investigated compounds in lymph did not exceed 5% of the doses given. The known fact that lymphatic drainage is regulated by arachidonate metabolites might suggest that NSAIDs differing in their lymphotropic properties could result in different responses of lymphatic vessels to an inflammatory fluid load.

Animals↗

[Structure of terminal lymphangion of the thoracic duct].

Peculiarities of terminal lymphangion wall in humans and dogs were studied in its different parts using various morphological methods. Main results were obtained with the use of a total preparation method after A.V. Borisov. Heterogenous distribution of myocytes in different regions of lymphangion (muscular cuff, valve sinus wall) was noted. In the terminal lymphangion myocytes from three anatomically and topographically different muscles: cuff muscle, tensor muscle of the distant valve, tensor muscle of the proximal valve (thoracic duct orifice valve). Some features of terminal lymphangion construction similar to those seen in other lymphangions as well as certain specific characteristics and species peculiarities, are described.

Adolescent↗

The effect of steroids on the circulating lymphocyte population. II. Studies of the thoracic duct lymphocyte population of the guinea pig after neonatal thymectomy and prednisolone treatment.

The effect of corticosteroids on the lymphatic tissue and circulating lymphocyte pool in the guinea pig has been studied. No signs of increased lymphocytolysis was seen and only after 1--2 weeks treatment with a long acting corticosteroid was the thymic cortex reduced and thymic weight decreased. Three hours after injecting a short acting steroid a 30--40 per cent reduction in the thoracic duct cell count was seen in both control and thymectomized animals. Restitution to pretreatment cell level was completed in 17 hours. Mononuclear cells in the blood were markedly depressed up to 40 hours. The changes in the circulating lymphocyte pool in the resistant guinea pig seem to be in principle the same as in the sensitive rat but less pronounced. It can be concluded that the lymphocyte level in the circulating pool is thymus dependent but restoration of the cell count after steroid treatment is independent of intact thymic function. This data supports the hypothesis of lymphocyte trapping and redistribution after a single steroid treatment.

Animals↗

Thoracic duct ligation and pericardectomy for treatment of idiopathic chylothorax.

Chylothorax is a devastating disease, and the success rates from either medical or surgical management are less than satisfactory. In some animals with chylothorax, a thickening of the pericardium occurs that is associated with chronic irritation induced by chyle. We hypothesized that pericardial thickening would lead to increased right-sided venous pressures and that abnormal venous pressures would act to impede the drainage of chyle via lymphaticovenous communications after thoracic duct (TD) ligation. We also hypothesized that serosanguineous effusions that occurred after TD ligation could effectively be treated or prevented by pericardectomy in affected animals. TD ligation plus pericardectomy was performed in 17 animals, and pericardectomy alone was performed in an additional 3 animals that presented during a 5.5-year period to the Texas A&M University (College Station, TX). Nineteen animals presented for an evaluation of idiopathic chylothorax (9 dogs and 10 cats), and 1 dog presented for serosanguineous pleural fluid after TD ligation that had been performed elsewhere. Echocardiography was normal in all animals, except for a subjectively thickened pericardium in 7 cats and 6 dogs. Clinical signs of pleural fluid accumulation resolved in 10 of 10 dogs and in 8 of 10 cats after surgery. The overall success rate for the surgical treatment of chylothorax (ie, the resolution of pleural fluid accumulation) in this study was 90% (100% in dogs and 80% in cats). These data suggest that TD ligation in conjunction with pericardectomy has a favorable outcome in animals with idiopathic chylothorax.

Animals↗

[Thoracic duct cyst--a case report].

The patient was a 59-year-old man with a 5-month history of cough, difficulty breathing, and palpitations while working. Initial examination at the internal medicine department of our hospital in August 1992 revealed a mass in the left side of the neck, and he was admitted for further examination and treatment. Preoperative investigations revealed a cystic lesion extending from the left neck area to the mediastinum. The mass was resected on August 13, 1992. Based on the intraoperative findings and postoperative histological examination, a diagnosis of thoracic duct cyst was made. The postoperative course was good and the patient was discharged after two weeks. This is extremely rare case, and the Trap door surgical approach proved useful for resection.

Humans↗

Temporal changes in the distribution of thoracic duct lymphoblasts to synovium and other tissues of rats with adjuvant-induced arthritis.

The distribution of lymphoblasts(lymphocytes in cell cycle) obtained from the central lymph of donor rats and transferred adoptively to syngeneic recipients has been shown previously to be influenced by the presence of arthritis in either donor or recipient rats. The intent of the present study was to examine patterns of distribution of lymphoblasts in the early period after transfer, when extravasation of donor lymphoblasts was expected to occur. Thoracic duct lymphoblasts labelled in vitro with [125I]-iododeoxyuridine were detected in recipient rats by external radiometry and autoradiography. Irrespective of donor status, fewer donor lymphoblasts accumulated in the feet of normal recipients when compared to arthritic recipients at 15 min, 2 h and 24 h after cell transfer.When recipients of similar disease status were compared, the percentages of injected lymphoblasts from normal and arthritic donors recovered in the feet were similar at 15 min and 2 h after transfer. The proportions of lymphoblasts recovered in the feetat 24 h after injection declined in normal recipients and arthritic recipients of cells from normal donor rats. Importantly,this decline did not occur when both the donor and the recipient were arthritic. In the hindpaws, donor lymphoblasts were located predominantly in the bone marrow, except in transfers between arthriticrats, when at 24 h they were predominantly in the synovium. At 15 min, lymphoblasts were detected within the lumen of vessels within synovium, whereas by 2 h extravasation of these cells was evident. In conclusion, lymphoblasts accumulate more readily in hindfeet that are inflamed. In the early hours after injection, lymphoblasts from normal and arthritic donors are recruited equally, but these early levels are only maintained for 24 hin the combination of arthritic donor and arthritic recipient. Adramatic change in the proportion of lymphoblasts located in synoviumat this later time suggests that a dynamic process of relocation,retention and/or local cell division maintains the numbers of arthritic donor cells in the latter combination.

Adjuvants, Immunologic↗

Free and conjugated catecholamines and serotonin in canine thoracic duct lymph: effects of feeding.

The source and fate of sulfoconjugated catecholamines present in plasma are not known. Sulfated norepinephrine has been shown to overflow together with free norepinephrine from a typical peripheral neuroeffector junction. Some released free norepinephrine is removed via the lymphatic system, but it is not known whether sulfated catecholamines are removed similarly. Serotonin, another biogenic amine, is released from the enterochromaffin cells into portal blood. The aims of the present study were to determine whether conjugated catecholamines and serotonin could be detected in thoracic duct lymph of dogs and to compare concentrations in lymph with those in samples of portal blood collected before and after the dogs were fed. A method is described for the extraction and purification of free and conjugated catecholamines and serotonin from lymph. In lymph and in plasma, there were similar concentrations of free (0.2-0.4 ng/ml) and conjugated (0.1-0.2 ng/ml) norepinephrine and of conjugated dopamine (0.2-1.0 ng/ml). The concentrations of free serotonin were much lower in lymph (0.1-0.2 ng/ml) than in portal blood (100-200 ng/ml). Small amounts of conjugated serotonin (0.1-0.4 ng/ml) were detected in lymph but were not detected in plasma. Feeding caused increases in concentration of conjugated dopamine in lymph and in plasma and small increases in the output of free norepinephrine and free and conjugated serotonin in lymph.

Amines↗

Migratory patterns of thoracic duct lymphocytes into bronchus-associated lymphoid tissue of immunized rats.

Lymphocytes continuously circulate between the bloodstream and lymphoid organs, and their migration into lymphatic tissues presumably occurs through selective mechanisms. Although bronchus-associated lymphoid tissue (BALT) is known as an inductive tissue of the common mucosal immune system, little is known about how effectively the lymphocytes in the blood vessels migrate into the BALT, thereby enabling the BALT to act as an effector tissue in the immunologic responses of the lungs. To analyze whether or not thoracic duct lymphocytes (TDL) from immunized and nonimmunized rats possess different migratory patterns to the BALT, 5-(6)-carboxyfluorescein diacetate succinimidyl ester (CFSE)-labeled TDL were injected into rats with BALT hyperplasia that was produced by intratracheal administration of TNP-KLH, and then the number of labeled cells in the BALT were examined by immunohistochemical methods. We studied the following three groups at 12 h after the injection: group A, intraintestinally immunized donors and intratracheally immunized recipients; group B, nonimmunized donors and intratracheally immunized recipients; group C (control group), nonimmunized donors and nonimmunized recipients. Time course studies 0.5, 4, 12, and 24 h after the injection were done in groups A and C. In a cytokinetic study, larger numbers of CFSE-labeled lymphocytes were found at 12 h and 24 h in group A than in group C. At 12 h after the injection, the absolute number of CFSE-labeled lymphocytes per BALT was significantly higher in group A than in group B (p < 0.05), and was lowest in group C. Histologically, there was a marked proliferation of high endothelial venules (HEV), with findings of adhesion and influx of lymphocytes inside the HEV in group A. These observations indicate that the immunized BALT actively recruits immunized TDL through a specific mechanism of lymphocyte-endothelium recognition in HEV, which partially explains the process of BALT development as an effector tissue for local immunity.

Animals↗

Angiotensin II infusion increases thoracic duct lymph flow in chronically catheterized sheep.

Both pregnancy and estrogen administration are associated with a decrease in the systemic vasculature pressor response to angiotensin II infusion; however, the lymphatic vessel system response is not clear. In the present study we infused angiotensin II to nine nonpregnant splenectomized ewes with 0.1, 10, or 1,000 ng X kg-1 X min-1 for a 5-min period at each dose. At the lowest dose the mean arterial pressure increased from 10 to 20% over base line. At the highest dose, the left thoracic duct flow rate peaked at 361% 10 min after the infusion was started, whereas arterial pressure peaked at 183% of the control value. Peak lymph flow occurred 4-6 min after the maximal increase in mean systemic arterial pressure. Neither hematocrit nor venous pressure were altered at any of the doses administered. This suggests that the interstitial fluid space pressure remained unchanged and that the increase in lymph flow was not secondary to fluid transfer from the intravascular system. We postulate, therefore, that the effect of angiotensin II in the increase of lymph flow rate is by direct action on the lymphatic vessels themselves.

Angiotensin II↗

Thoracic duct lymph flow responses to hemorrhage in the ovine fetus.

Blood volume returns toward normal after hemorrhage much more rapidly in the fetus than in the adult due to a rapid entry of fluid and plasma proteins into the fetal circulation. One potential source of fetal fluids and plasma proteins is the lymphatic system, since basal lymph flow rate and interstitial protein concentration are high in the fetus. Furthermore, studies in adults suggest that lymph flow rate may increase following hemorrhage. To test the hypothesis that hemorrhage induces an increase in lymph flow in the fetus, 15 late-gestation ovine fetuses underwent left thoracic duct catheterization with low-resistance catheters and were studied 5 or more days after surgery at 134 +/- 1 (SE) days gestation. The protocol included three successive 30-min periods: control, hemorrhage, and recovery. During the first 5 min of the hemorrhagic period, 61 +/- 4 ml of fetal blood were removed. The blood was reinfused over the first 5 min of the recovery period. After the hemorrhage, fetal arterial pressure, venous pressure, and heart rate decreased (analysis of variance, P < 0.001). These variables significantly increased above basal levels following blood reinfusion. Fetal hematocrit (P < 0.001) and plasma protein concentration (P < 0.05) also decreased after the hemorrhage and returned to control values after the reinfusion. Fetal lymph flow rate was 0.55 +/- 0.06 (SE) ml/min before the hemorrhage and decreased by a maximum of 30.3 +/- 6.3% (P < 0.001) at 8 min after the end of the hemorrhage. Lymph flow rate was reduced by an average of 19.1 +/- 6.6% during the hemorrhagic period and returned to prehemorrhage levels following blood reinfusion.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗