Cardiorespiratory and cellular changes with interleukin 2 infusion in sheep

Recombinant interleukin 2 (rIL-2) administration, a new form of therapy for patients with far-advanced cancer, is associated with a "third space" syndrome, i.e., pulmonary edema, respiratory distress, and hypoxemia, which limits the dose and duration of treatment. To extend our knowledge regarding this toxicity, we established a sheep chronic lung lymph fistula model and measured hemodynamics, arterial blood gases, caudal mediastinal (lung) lymph flow (QL), and blood and lung lymph cellular changes before, during, and after (recovery) a 3-day continuous rIL-2 infusion (9 x 10(5) U/kg). Moderate systemic hypotension, mild pulmonary hypertension, and an increase in alveolar-arterial PO2 gradient was present on day 3 of rIL-2 infusion. QL increased from a base line of 1.9 +/- 0.2 to a maximum of 4.3 +/- 1.1 ml/15 min on day 3 of rIL-2 infusion. At no time was there a change in lymph-to-plasma protein ratio. The leukocyte count increased significantly to 16.1 +/- 4.5 x 10(3) cells/mm3 at recovery day 1. The percentage of blood lymphocytes decreased significantly by day 1 of rIL-2 infusion, returned to base-line levels on day 3, and significantly increased on day 2 of recovery. Lung lymph lymphocytes decreased significantly on days 1 and 2 of rIL-2 infusion. There was a shift in their size; i.e., their area increased from 32 +/- 7 to 57 +/- 19 micron 2 (P less than 0.05) by day 2 of rIL-2 infusion. By day 1 of recovery, lung lymph lymphocyte counts increased significantly.(ABSTRACT TRUNCATED AT 250 WORDS)     

Amino acid composition of the lymph and blood in fever reactions of different durations

The amino acid composition of the thoracic duct lymph and blood following fever reactions (FR) of various duration has been studied in the experiments on rabbits. The experiments have shown that some changes in protein metabolism in FR are primarily manifested in amino acid lymph composition. Irrespective of FR duration the amino acid content in the lymph almost always increases, which confirms the opinion concerning catabolic process predominance in protein metabolism during FR. The lack of "cumulative" conditions in the blood, amino acid dilution in the large volume of the circulating blood, as well as the increase of vascular permeability during FR cause less marked increase in amino acid content in the blood than in the lymph.     

Cytotoxicity of effector cells of the peripheral blood, lymph nodes and spleen in Hodgkin's disease

The mononuclear cells and T-lymphocytes of the blood, spleen and lymph nodes from 83 patients with Hodgkin's disease and 50 healthy donors were tested in assays for lectin-dependent (LD) and natural killer (NK) cytotoxic activity (CTA). On an average, peripheral blood T cell LD-CTA of patients did not differ from that of the donors. However, the CTA appeared to be dependent on the stage of the disease; in the IVth stage LD-CTA was decreased 2-fold. The LD-CTA was also dependent on the histological type of disease and the lowest level of LD-CTA (50% of the control level) was associated with the "lymphocyte depletion" type. The CTA of T-lymphocytes from the affected areas of the patients' spleen was more marked than that of the unaffected areas. Spleen cell CTA showed no other correlations. The CTA of lymphocytes from the affected lymph nodes was drastically lower than CTA of blood and spleen lymphocytes. The NK activity of the patients' blood and spleen lymphocytes was twice as less as the control level (healthy donors) and did not correlate with a stage and/or a histological type of the disease. It was assumed that in Hodgkin's disease the specific antitumor immunity remains mostly within normal and is decreased only in the last, terminal stage of the disease.     

Cardiopulmonary effects of recombinant interleukin-2 infusion in sheep

The systemic administration of recombinant interleukin-2 (rIL-2) with or without lymphokine-activated killer (LAK) cells, a new treatment for patients with advanced cancer, is associated with a presumed "third-space" syndrome. To further define the extent and time course of this toxicity, we established a chronic sheep model and monitored changes in systemic and central vascular pressures, cardiac function, and gas exchange during a 72-h continuous intravenous infusion of rIL-2 at a total dose of 5 (group 3) or 9 x 10(5) U/kg (group 4). At 72 h, caudal mediastinal lymph flow, histology, and extravascular lung water-to-dry lung weight ratio (EVLW/DLW) were obtained. During the rIL-2 infusion there was a dose-dependent significant decrease in systemic blood pressure and arterial Po2 and an increase in core temperature. In group 4, pulmonary arterial pressure increased from a base line of 13 +/- 5 to 21 +/- 6 mmHg (P less than 0.05). Lung lymph flow was significantly increased in groups 3 and 4 compared with animals receiving 0.9% NaCl or excipient infusions (groups 1 and 2). EVLW/DLW values were elevated in groups 3 and 4 (P less than 0.01). In animals receiving rIL-2, histological evaluation revealed a dose-dependent infiltration of lung tissue by lymphoblastoid cells that stained esterase negative. We conclude that rIL-2 infusion in doses comparable to those given to humans results in alterations in systemic and central hemodynamics, gas exchange, high-protein lung lymph flow, and infiltration of lymphoblastoid cells into the lung parenchyma.     

Radioactive iodoprotein in thyroid lymph and blood

1. Samples of thyroid and non-thyroid lymph and of thyroid and peripheral venous blood were obtained from primates and cats that had previously been given radioactive iodine. The distribution of the organic radioiodine between the protein and non-protein fractions in these samples was determined. 2. The proportion of the organic radioiodine in the form of iodoprotein was assessed by paper chromatography, acid-ethanol precipitation, hot-butanol washing, column chromatography and separate estimation of iodotyrosines after enzymic hydrolysis. 3. In thyroid lymph the relative proportion of the organic radioiodine in the form of iodoprotein was 75–98%; in blood it was much lower, probably no more than 6–7%. The absolute concentration of iodoprotein radioactivity also was considerably greater in thyroid lymph than in blood. 4. Enzymic hydrolysis of the protein of the thyroid lymph yielded a pattern of iodoamino acids that corresponded closely with that obtained after hydrolysis of protein extracted from the thyroid gland itself. 5. It can be concluded that the iodoprotein in thyroid lymph consists mainly of thyroglobulin or a closely related compound.     

Transferase contents in lymph and blood in fever reaction]

The aim of the present investigation was the study of the content of alanine, asparagine-transaminases, gamma-glutamyl transferase and their isoenzymes, as well as leucine aminotransferase in the lymph of thoracic duct, hepatic and intestinal lymph and peripheral blood in dynamics of fever reaction of various duration in the experiments on rabbits. Irrespective of its duration, the fever was followed by a significant activation of the enzymes in the body fluids. However, in many-day fever reaction, a rise of enzymes level in the lymph was more prolonged than that in the blood. The above studies make it possible to assume that the released enzymes in fever reaction are primarily resorbed by lymphatic capillaries and their activity indices in the blood serum are largely evidenced by the transport function of the lymphatic system.     

Chylomicrons Promote Intestinal Absorption and Systemic Dissemination of Dietary Antigen (Ovalbumin) in Mice

Background

A small fraction of dietary protein survives enzymatic degradation and is absorbed in potentially antigenic form. This can trigger inflammatory responses in patients with celiac disease or food allergies, but typically induces systemic immunological tolerance (oral tolerance). At present it is not clear how dietary antigens are absorbed. Most food staples, including those with common antigens such as peanuts, eggs, and milk, contain long-chain triglycerides (LCT), which stimulate mesenteric lymph flux and postprandial transport of chylomicrons through mesenteric lymph nodes (MLN) and blood. Most dietary antigens, like ovalbumin (OVA), are emulsifiers, predicting affinity for chylomicrons. We hypothesized that chylomicron formation promotes intestinal absorption and systemic dissemination of dietary antigens.

Methodology/Principal Findings

Absorption of OVA into MLN and blood was significantly enhanced when OVA was gavaged into fasted mice together with LCT compared with medium-chain triglycerides (MCT), which do not stimulate chylomicron formation. The effect of LCT was blocked by the addition of an inhibitor of chylomicron secretion, Pluronic L-81. Adoptively transferred OVA-specific DO11.10 T-cells proliferated more extensively in peripheral lymph nodes when OVA was gavaged with LCT than with MCT or LCT plus Pluronic L-81, suggesting that dietary OVA is systemically disseminated. Most dietary OVA in plasma was associated with chylomicrons, suggesting that these particles mediate systemic antigen dissemination. Intestinal-epithelial CaCo-2 cells secreted more cell-associated, exogenous OVA when stimulated with oleic-acid than with butyric acid, and the secreted OVA appeared to be associated with chylomicrons.

Conclusions/Significance

Postprandial chylomicron formation profoundly affects absorption and systemic dissemination of dietary antigens. The fat content of a meal may affect immune responses to dietary antigens by modulating antigen absorption and transport.     

Tissue-specific expression of LeY antigen in high endothelial venules of human lymphoid tissues

In this study, we demonstrated that the anti-Le^Yantibody (BM-1) especially reacted with high endothelial venules (HEVs) in peripheral lymph nodes of blood group O individuals. The Le^Yexpression on HEVs showed a unique tissue-specific pattern, i.e., a large amount of the Le^Yexpression in peripheral lymph nodes and no or small amounts in mesenteric lymph node. Statistical analysis showed that there was the significant difference between the percentage of Le^Y-positive HEVs in peripheral lymph nodes and mesenteric lymph nodes. No expression of Le^Ywas observed in vessels of Payer's patch, thymus, spleen and other non-lymphoid organs. In blood group A or B individuals, the reactivity between HEVs and anti-Le^Yantibody increased after enzyme digestion with -N-acetylgalactosaminidase or -galactosidase. These findings show that the expression of difucosylated blood group ABH antigens are especially expressed on HEVs in peripheral lymph nodes. Furthermore, the tissue-specific pattern suggests that these antigens may be related to intercellular adhesion between lymphocytes and HEVs.     

Lymph heart musculature in birds

Development and innervation of the lymph heart musculature of chicken, emu, rhea, and duck was studied by electron microscopy at post-hatch ages from 3 days to adulthood. Development of innervation was monitored by acetylcholinesterase staining. Horseradish peroxidase was used to determine the extent of the transverse tubule network. Chickens were unusual among these birds in that lymph heart myocytes had already undergone a definitive differentiation and degeneration by 3 days. In ducks and ratite birds, lymph heart myocytes more slowly but progressively differentiate a cytomorphology that does not conform in all characteristics to cardiac or skeletal muscle and even resembles in some aspects, smooth muscle. Myofibrils become the dominant cytoplasmic structure, transverse tubules form "internal couplings" with agranular reticulum cisternae, and "external couplings" are formed between myocytes at myomyal junctions. The myomyal junctions also contain AChE-positive reaction product and some subplasmalemmal vesicles that lack a dense core. The lymph heart myocardium of ducks of 2 weeks demonstrated mitotic figures. In adult ducks the myosatellite cell numbers diminish and a characteristic pattern of myocyte degeneration appears. In juvenile ducks and ratites some myocytes differentiate to conductile cells, much as the conductile myocytes and myofibers of the blood heart. The lymph heart innervation is described, and the role of nerve in differentiation and maintenance of myocyte morphology in the lymph heart is discussed.     

Enzyme activities in thoracic duct lymph and plasma of anaesthetized, conscious resting and exercising dogs

The significance of changes in lymph flow for the extracellular distribution and transport of cellular enzymes and for the level of enzyme activities in plasma was investigated. Specimens of thoracic duct lymph were obtained from an extracorporal lymph shunt in anaesthetized, conscious resting and treadmill exercising dogs (6 km X h-1 for 1 h) The activity of 10 enzymes and of protein content in lymph and plasma were studied, as well as lymph flow, lymphatic transport, and the lymph-plasma ratio of these compounds. Lactate, pH, and blood gases were monitored in venous blood. Lymph flow of 0.80 ml X min-1 in anaesthetized dogs more than doubled (to 1.86 ml X min-1) when the animals were conscious and resting. In anaesthetized dogs lymph enzyme activity was higher only for enzymes of predominately hepatic origin, such as choline esterase (CHE) and alanine aminoferase (ALAT), and was lower for aspartate aminotransferase (ASAT) and aldolase (ALD). In conscious dogs, due to activation of the skeletal muscle "tissue pump", lymphatic transport of enzymes with rather high activity in skeletal muscle, and of protein, is significantly enhanced. Enzyme activities in plasma, however, did not differ between the groups. Lymph-plasma activity ratios higher than one were found for lactate dehydrogenase (LDH), malate dehydrogenase (MDH), ASAT, creatine kinase (CK), ALD, and phosphohexose isomerase (PHI). Exercise stimulated lymph flow up to 4.9 ml X min-1, and increased the lymphatic activities of those enzymes with a lymph-plasma ratio higher than unity, these enzymes increasing in the plasma due to the highly increased lymphatic transport.(ABSTRACT TRUNCATED AT 250 WORDS)     

Immunohistochemical analysis of human peripheral blood and lymphoid tissues using monoclonal antibodies immunoreactive with non-lymphoid cells

Summary Immunoperoxidase methods were used to study human peripheral blood and lymphoid tissues using a panel of monoclonal antibodies to non-lymphoid cells. The majority of peripheral blood monocytes were immunoreactive for LeuM1, LeuM2, LeuM3 and LeuM5. Rare peripheral blood monocytes were immunoreactive for R4/23. The different antibodies showed characteristic patterns of immunoreactivity in peripheral lymphoid tissues. LeuM1 was immunoreactive with scattered cells in the paracortex of lymph node and tonsil and with many cells in the marginal zone of the spleen. LeuM2 was immunoreactive with endothelial cells in lymph node and tonsil. A few cells in the red pulp of the spleen were immunoreactive for LeuM2. LeuM3 and R4/23 showed distinctive immunoreactivity in germinal centers of secondary follicles, giving a lacy pattern. LeuM3 was also immunoreactive with endothelium in lymph node and tonsil and with sinus lining cells in lymph node. LeuM5 was immunoreactive with macropages in the germinal center, fibroblastic reticulum cells in the mantle zone and interdigitating reticulum cells in the paracortex of lymph node and tonsil.     

Flow and composition of lymph from the ovary and uterus of cows during pregnancy

Ovarian or uterine lymph was collected continuously for periods of up to 25 days from 16 cows cannulated at stages of pregnancy ranging from 96 to 278 days post coitum. Blood samples were taken acutely from the ovarian and uterine veins during surgery and periodically from the jugular vein during the course of lymph collection. The flow rate and cell content of lymph was measured and blood and lymph plasma samples were analysed for progesterone, pregnenolone, pregnenolone sulphate, androstenedione, testosterone, oestrone, oestrone sulphate, oestradiol-17 beta, prostaglandin (PG) F-2 alpha, total protein and albumin. There was a high flow rate of protein-rich lymph from luteal ovaries with rates up to 101.7 ml/h occurring in individual lymphatics over short periods. Peripheral ovarian and uterine lymph contained a low concentration of cells (mean less than 10(5) cells/ml) comprising about 82-87% lymphocytes, 11-14% macrophages and monocytes and 2-4% other cells. At all stages of pregnancy, the concentration of progestagens and androgens was higher in ovarian lymph than in uterine lymph or blood plasma. The differences were greatest for progesterone and androstenedione which occurred at 200-fold and 60-fold greater concentration respectively in ovarian lymph than in jugular plasma. When serial 10 min samples were collected over a 12-h period, the concentration and output of progesterone in ovarian lymph varied in a phasic manner, ranging from 3.5 to 7.6 microM and from 31.7 to 293.1 nmol/h respectively. There was a positive correlation between the output of progesterone in lymph and the progesterone concentration in jugular blood samples taken every 20 min. During most of pregnancy there was little difference between the concentration of oestrogens in ovarian lymph, ovarian venous plasma and jugular plasma but, during the 3-5 days before calving, these hormones occurred at slightly higher concentration in ovarian lymph. Apart from pregnenolone and androstenedione, all steroids occurred at lower concentrations in uterine lymph than in jugular plasma. Shortly before parturition there was an abrupt increase in the concentration of PGF-2 alpha in uterine lymph. Lymph reflects more accurately the milieu of tissue cells than efferent blood and further analysis of differences in the concentration of substances in lymph relative to the output in the ovarian and uterine arterial and venous blood may lead to the identification of factors important in local regulatory mechanisms in the reproductive tract.     

Ratio of Metastatic to Examined Lymph Nodes,a Helpful Staging System and Independent Prognostic Factor of Esophagogastric Junction Cancer

Background

The incidence of the esophagogastric junction cancer is growing rapidly. The purpose of this study is to clarify the outcome of the ratio between metastatic and examined lymph nodes in esophagogastric junction cancer patients with or without 7 examined lymph nodes.

Methods

A total of 3,481 patients who underwent operation are identified from the Surveillance, Epidemiology, and End Results database. Different lymph nodes resected groups are analyzed to test the lymph nodes ratio factor.

Results

There are 2522 patients with 7 or more lymph nodes resected and 959 patients with less than 7 lymph nodes resected. Lymph nodes ratio and lymph node involvement are independent prognostic factors. But the lymph nodes ratio categories have a better prognostic value than the lymph node involvement categories. Compared with lymph node involvement categories, lymph nodes ratio categories represent patients with more homogeneous overall survival rate.

Conclusions

This study defines that the lymph nodes ratio is an independent prognostic factor for esophagogastric junction cancer. The lymph nodes ratio can prevent stage migration and may be a helpful system to predict the prognosis of esophagogastric junction cancer patients.     

Immunohistochemical analysis of human peripheral blood and lymphoid tissues using monoclonal antibodies immunoreactive with non-lymphoid cells

Immunoperoxidase methods were used to study human peripheral blood and lymphoid tissues using a panel of monoclonal antibodies to non-lymphoid cells. The majority of peripheral blood monocytes were immunoreactive for LeuM1, LeuM2, LeuM3 and LeuM5. Rare peripheral blood monocytes were immunoreactive for R4/23. The different antibodies showed characteristic patterns of immunoreactivity in peripheral lymphoid tissues. LeuM1 was immunoreactive with scattered cells in the paracortex of lymph node and tonsil and with many cells in the marginal zone of the spleen. LeuM2 was immunoreactive with endothelial cells in lymph node and tonsil. A few cells in the red pulp of the spleen were immunoreactive for LeuM2. LeuM3 and R4/23 showed distinctive immunoreactivity in germinal centers of secondary follicles, giving a "lacy" pattern. LeuM3 was also immunoreactive with endothelium in lymph node and tonsil and with sinus lining cells in lymph node. LeuM5 was immunoreactive with macrophages in the germinal center, fibroblastic reticulum cells in the mantle zone and interdigitating reticulum cells in the paracortex of lymph node and tonsil.     

Oxidation of cholinesterase-inhibiting pesticides: A simple experiment to illustrate the role of bioactivation in the toxicity of chemicals

A simple undergraduate laboratory experiment that can be used in Biochemistry and Toxicology courses to illustrate the importance of metabolic reactions in the toxicity of chemical substances is reported. It involves the experimental confirmation that oxidized phosphorothionate esters, commonly used as insecticides, are stronger cholinesterase inhibitors and therefore exhibit higher toxicity than do their sulphur analogs starting from which the first are formed by in vivo oxidative desulphuration. Two separated aliquots of a bovine blood sample are incubated with parathion and paraoxon, its oxygen analog, and compared for cholinesterase activity with "normal" blood. Previously, a standard sample of paraoxon was obtained by oxidation of the thiono group of parathion with bromine vapour by reaction TLC. The comparison of the inhibitory capacity of both compounds is made by a colorimetric procedure using acetylthiocholine as substrate of the enzyme and 5,5'-dithiobis-(2-nitrobenzoic acid) as chromogen.     

Local eosinophil- and mast cell-related responses in abomasal nematode infections of lambs

Abstract Eosinophil numbers in peripheral blood and eosinophil potentiating activity(EPA) and sheep mast cell protease (SMCP) in efferent gastric lymph were monitored in lambs during infections with Ostertagia circumcincta . Worm burdens, eosinophil numbers in bone marrow, abomasal mucosa and gastric lymph node, as well as mast cell numbers and SMCP concentrations in mucosa and mucus, were determined in post mortem samples. In naive lambs, high and relatively uniform worm burdens were present 10 days after primary infection and these were associated with only mild blood and tissue eosinophilia. By day 21 worm burdens were markedly lower and more variable. There was more evidence of eosinophil and mast cell accumulation in mucosa, and numbers in bone marrow were also higher than on day 10. However, neither EPA nor SMCP were detectable in lymph. By contrast, EPA and SMCP were present in substantial amounts in draining lymph within 48 h of challenge (secondary) infection of previously exposed lambs. EPA was inversely related to worm burdens recovered on day 10, as were abomasal mucosal and mucus SMCP concentrations. Elevated eosinophil numbers were also consistently detected in blood, bone marrow, mucosa and gastric lymph node. The results suggest that host immune defence against secondary, but not primary, exposure to O. circumcincta involves a rapidly mobilised local inflammatory component.     

STUDIES ON LYMPHOCYTES

Continuous extracorporeal irradiation of the circulating blood (ECIB) of from 3 to 501/2 hr duration was used to study in the calf the differential depletion of lymphocytes from spleen, lymph nodes and thymus as compared to blood and thoracic duct lymph. The cell content of tissues was measured by planimetry and/or test point analysis. Lymphocyte depletion by ECIB from various lymphoreticular organs, and from different areas within a given organ, was less than in the circulating blood or the thoracic duct lymph and varied from one site of a lymphoreticular organ to another. The degree of depletion with time followed an exponential function with at least two components. The first component corresponded to a relatively rapid fall and the second to a very slow reduction in lymphocyte content. The former is related to the elimination of an easily mobilizable pool of lymphocytes while the latter corresponds to a more sessile mass of lymphocytes which exchange with blood lymphocytes very slowly. Elimination of the easily mobilizable pool of lymphocytes by ECIB from all tissues studied was observed within 10–15 hr, indicating that the rate of exchange with blood is similar for this group of cells in various lymphoreticular tissues. The size, however, of the easily mobilizable vs the more sessile pools of lymphocytes may vary considerably, the best estimates for the former being as follows (in per cent of total lymphocyte mass): lymph node medulla, less than 10%; lymph node cortex plus paracortical zone, 18% (depletion mainly paracortical); red pulp of the spleen, 37%; densely populated white pulp of the spleen, 55%; and loosely populated white pulp of the spleen, 60%. In comparison, the approximate fractions of lymphocytes originating fromthe easily mobilizable pools in various lymphoreticular tissues plus the cells already circulating a t the onset of EClB correspond to 64% for the thoracic duct lymph and 78% for the circulating blood respectively. These findings are discussed in relation to production, recirculation and life span of lymphocytes, and immune reactions.     

Radiosensitivity of T and B lymphocytes. IV. Effect of whole body irradiation upon various lymphoid tissues and numbers of recirculating lymphocytes.

Groups of 10-week-old female CBA/J mice were exposed in whole body fashion to 0,5,50, and 500 rads and sacrificed in serial fashion 1,3,5,7,9,15, and 30 days after irradiation for morphologic evaluation of thymus, spleen, lymph node, and Peyer's patch, and assessment of the relative numbers of thymus-derived (T) and bone marrow-derived (B) cells in these tissues. The absolute and relative numbers of recirculating T and B cells mobilizable by thoracic duct cannulation were also determined and compared with similar determinations with respect to peripheral blood lymphocytes. B cell depletion occurred more quickly and was more pronounced in spleen and lymph node than T cell depletion at all three exposure doses. Depletion of T and B cells was roughly equal in peripheral blood and thoracic duct lymph. When present, regeneration of the T cell component occurred more rapidly than did B cell restoration. The latter often was incomplete at the time of the final sacrifice (day 30). PHA-responsive and Con A-responsive cells also appeared to differ with respect to the kinetics of cell death after whole body irradiation.     

Lymphocyte subpopulations in lymph nodes and peripheral blood: a comparison between patients with stable angina and acute coronary syndrome

Objective

Atherosclerosis is characterized by a chronic inflammatory response involving activated T cells and impairment of natural killer (NK) cells. An increased T cell activity has been associated with plaque instability and risk of acute cardiac events. Lymphocyte analyses in blood are widely used to evaluate the immune status. However, peripheral blood contains only a minor proportion of lymphocytes. In this study, we hypothesized that thoracic lymph nodes from patients with stable angina (SA) and acute coronary syndrome (ACS) might add information to peripheral blood analyses.

Methods

Peripheral blood and lymph nodes were collected during coronary by-pass surgery in 13 patients with SA and 13 patients with ACS. Lymphocyte subpopulations were assessed by flow cytometry using antibodies against CD3, CD4, CD8, CD19, CD16/56, CD25, Foxp3, CD69, HLA-DR, IL-18 receptor (R) and CCR4.

Results

Lymph nodes revealed a lymphocyte subpopulation profile substantially differing from that in blood including a higher proportion of B cells, lower proportions of CD8⁺ T cells and NK cells and a 2-fold higher CD4/CD8 ratio. CD4⁺CD69⁺ cells as well as Foxp3⁺ regulatory T cells were markedly enriched in lymph nodes (p<0.001) while T helper 1-like (CD4⁺IL-18R+) cells were more frequent in blood (p<0.001). The only significant differences between ACS and SA patients involved NK cells that were reduced in the ACS group. However, despite being reduced, the NK cell fraction in ACS patients contained a significantly higher proportion of IL-18R⁺ cells compared with SA patients (p<0.05).

Conclusion

There were several differences in lymphocyte subpopulations between blood and lymph nodes. However, the lymphocyte perturbations in peripheral blood of ACS patients compared with SA patients were not mirrored in lymph nodes. The findings indicate that lymph node analyses in multivessel coronary artery disease may not reveal any major changes in the immune response that are not detectable in blood.     

Interactions of noradrenalin and tumour necrosis factor alpha, interleukin 4 and interleukin 6 in the control of lipolysis from adipocytes around lymph nodes.

The contributions of inflammatory and immunosuppressive cytokines and noradrenalin to the control of lipolysis in adipocytes surrounding and remote from lymph nodes were investigated in healthy adult guinea-pigs. A few hours after excision from fasting animals, spontaneous lipolysis in adipocytes from around the popliteal and mesenteric lymph nodes and omental "milky spots" was significantly lower than in those from elsewhere in the same depots, and much lower than in perirenal, epididymal or parametrial adipocytes. The perinodal adipocytes were consistently more sensitive to noradrenalin at 10(-8), 10(-7)and 10(-5) M, and their maximum rate of lipolysis was higher. They also responded more strongly to pre-incubation for 24 h with tumour necrosis factor alpha interleukin 6 and interleukin 4 than those elsewhere in the same depots. Tumour necrosis factor alpha and interleukin 6 applied alone stimulated lipolysis, but combined with interleukin 4, they suppressed glycerol release, especially in perinodal adipocytes, thereby creating large within-depot differences. These cytokines had minimal effects on lipolysis in perirenal or gonadal adipocytes.The authors conclude that adipocytes surrounding lymph nodes contribute little to whole-body energy supply during fasting, but are more sensitive than all others to cytokines and to noradrenalin, having higher maximum but lower minimum rates of lipolysis. These properties equip perinodal adipocytes for local interactions with lymphoid tissue.