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PubMed2004

Validation of immune function testing during a 4-week oral toxicity study with FK506.

Assessment of the immune system's capability to respond to antigens with the generation of specific antibodies, whilst under the influence of a test article, is required in toxicity tests according to the European guideline for repeated dose toxicity testing of medicinal products. The purpose of this study in rats was to validate methodology for the determination of Keyhole Limpet Haemocyanin (KLH)-specific antibodies under the influence of an immunologically active compound. The immunosuppressant FK506, commercially available as Prograf, was administered orally (gavage) to five rats per sex per group at dosages of 0.5mg/kg per day or 3mg/kg per day, for a period of 4 weeks. On days 14 and 22, KLH was administered subcutaneously, with an adjuvant (AluGel), to the two treated groups and a control (i.e. without FK506 treatment) approximately 1h following administration of FK506. Terminal investigations included haematology parameters, titration of KLH-specific antibodies in serum (ELISA), macroscopic pathology, spleen and thymus weights, immunophenotyping of splenocytes (FACS analysis) and histopathology of the lymphatic tissues. At 3mg/kg per day a minimal reduction of subcutaneous KLH-induced granuloma formation and a moderate to marked reduction of germinal centre development (axillary lymph node and spleen) were observed. Reduced CD4+ (T-cell) counts were found in the spleen of males, consistent with a suppressed production of KLH-specific antibodies (IgG in both sexes, IgM in males only) and a higher incidence of atrophy in the periarteriolar lymphoid sheaths of males. Slight-to-moderate lymphopenia was present in both sexes at 3mg/kg per day. These findings are consistent with the known pharmacological activity of FK506. In conclusion, determination of antibody titres following immunisation of rats with KLH, with concurrent exposure to a drug, appears to be a valid method in the context of the immunotoxicity evaluation required by European regulation.

Animals↗
PubMed1999

Alterations in immune functions during normal aging and Alzheimer's disease.

It is thought that aging induces immune changes, which are related to the pathophysiology of Alzheimer's disease (DAT). In this study, the total number of leukocytes, white blood cell differentiation, mitogen-induced lymphocytic proliferation, neutrophil phagocytosis and superoxide release, and prostaglandin E2 (PGE2) production by mitogen-stimulated whole blood cultures were comparatively investigated between healthy adults (range 22-45 years) and healthy elderly volunteers (range 70-91 years), and between DAT patients (range 56-94 years) and age-matched control subjects. Healthy elderly volunteers showed significantly lower phytohemagglutinin (PHA)-induced lymphocyte proliferation and percentage and absolute number of basophils than young volunteers. In normal volunteers, there were significant and negative correlations between age and the number of basophils. Patients with DAT showed a trend toward significantly higher PHA-induced lymphocyte proliferation and significantly decreased percentage and absolute number of large unstained cells than healthy volunteers. In DAT patients, the total number of leukocytes and the percentage and number of neutrophils were positively correlated with age. All other immune-inflammatory variables were not significantly altered either by the aging process or DAT. The present study suggests that aging and DAT may differently affect some immune variables.

Adult↗
PubMed2005

Conjugated linoleic acid enhanced the immune function in broiler chicks.

This study was undertaken to investigate the growth performance and immune responses of broiler chicks fed diets supplemented with conjugated linoleic acid (CLA). Two hundred and forty day-old Arbor Acre male broiler chicks were randomly allotted into four dietary treatments with different inclusion levels of CLA (0, 2.5, 5.0 or 10.0 g pure CLA/kg) for 6 weeks. Growth performance, lysozyme activity, peripheral blood mononuclear cell (PBMC) proliferation, prostaglandin E2 (PGE2) synthesis and antibody production were investigated. There were no significant differences in growth performance among treatments (P>0.05). Chicks fed 10.0 g CLA/kg diet produced 40 % and 49 % more lysozyme activity in serum and spleen than the control group at 21 d of age (P<0.05). Dietary CLA enhanced the PBMC proliferation in response to concanavalin A at the age of 21 and 42 d (P<0.05). Systemic and peripheral blood lymphocytic synthesis of PGE2 in chicks fed 10.0 g CLA/kg diet was significantly decreased by 57 % and 42 % compared to chicks fed control diet (P<0.05). Antibody production to sheep red blood cell and bovine serum albumin were elevated in either 2.5 or 10.0 g CLA/kg dietary treatments (P<0.05). The results indicated dietary CLA could enhance the immune response in broiler chicks, but did not alter the growth performance.

Animals↗
PubMed1991

Restoration of immune functions after chemotherapy.

A paradigmatic case in which anticancer chemotherapy could paradoxically lead to immune restoration is reported. A patient with hairy cell leukemia was unsuccessfully treated with alpha-interferon. Treatment had to be withdrawn because of unusual toxicity and therapy with cytotoxic drugs had to be administered. Not only did the anticancer agents produce a complete remission of the disease, but the immunological profile of the patient improved. This case report raises the problem of the interference of chemotherapy with the immune system in cancer patients.

Antineoplastic Agents↗
PubMed1993

[Influence of smoking on red cell immune functions in highland adult men].

Formations of red cell C3b receptor rosette, red cell immune complex and helping tumour red cell rosette were assayed in 194 smokers and 66 non-smokers. Results showed red cell C3b receptor rosette and helping tumour red cell rosette formation in smokers was lower than in non-smokers (P < 0.01 and P > 0.05, respectively), but red cell immune complex formation in smokers was higher than in non-smokers. Red cell C3b rosette formation decreased with the quantity and duration of smoking. It suggested heavily smoking for a long period could influence the capabilities of red cell to clear out immune complex and to adhere and attack the tumour cells.

Adolescent↗
PubMed2006

Lidocaine depresses splenocyte immune functions following trauma-hemorrhage in mice.

Traumatic and/or surgical injury as well as hemorrhage induces profound suppression of cellular immunity. Although local anesthetics have been shown to impair immune responses, it remains unclear whether lidocaine affects lymphocyte functions following trauma-hemorrhage (T-H). We hypothesized that lidocaine will potentiate the suppression of lymphocyte functions after T-H. To test this, we randomly assigned male C3H/HeN (6-8 wk) mice to sham operation or T-H. T-H was induced by midline laparotomy and approximately 90 min of hemorrhagic shock (blood pressure 35 mmHg), followed by fluid resuscitation (4x shed blood volume in the form of Ringer lactate). Two hours later, the mice were killed and splenocytes and bone marrow cells were isolated. The effects of lidocaine on concanavalin A-stimulated splenocyte proliferation and cytokine production in both sham-operated and T-H mice were assessed. The effects of lidocaine on LPS-stimulated bone marrow cell proliferation and cytokine production were also assessed. The results indicate that T-H suppresses cell proliferation, Th1 cytokine production, and MAPK activation in splenocytes. In contrast, cell proliferation, cytokine production, and MAPK activation in bone marrow cells were significantly higher 2 h after T-H compared with shams. Lidocaine depressed immune responses in splenocytes; however, it had no effect in bone marrow cells in either sham or T-H mice. The enhanced immunosuppressive effects of lidocaine could contribute to the host's enhanced susceptibility to infection following T-H.

Animals↗
PubMed1982

Studies of immune functions of patients with chronic hepatitis.

Peripheral T cells from patients with chronic active hepatitis (CAH) showed a significantly decreased suppressor effect (or increased helper effect) on allogeneic B cell differentiation into Ig-producing cells (Ig-PC) (p less than 0.05). After irradiation of T cells to eliminate suppressor influences, mean spontaneous helper activity of CAH was not different from that of healthy subjects, indicating that spontaneous helper activity of CAH was normal. Concanavalin A (Con A)-induced suppressor cell activity was significantly decreased in CAH (p less than 0.01, 9 defective cases out of 18 patients). Minor defect of Con A-induced suppressor activity was also found in some patients with chronic persistent hepatitis (CPH) (2 defective cases out of 14 patients). Autologous mixed lymphocyte reaction (AMLR) was significantly decreased in patients with CAH (p less than 0.005). Spontaneous suppressor or Con A-induced suppressor activity was not different statistically between HBsAg-positive and HBsAg-negative cases. Finally, we demonstrated a presence of a serum factor(s) that can decrease Con A-induced suppressor cell function of healthy subjects in 7 of 21 patients with CAH and 2 of 14 CPH. Our results suggest that defective suppressor cell function likely attributable to serum factor(s) may reflect altered immune responses of CAH.

B-Lymphocytes↗
PubMed2004

Dietary restriction and immune function.

Dietary restriction is beneficial in preventing a multitude of diseases, many of which may involve the immune system in their etiology. Recent reports examining dietary restriction focused on T lymphocytes and macrophages. Dietary restriction delays the onset of T-lymphocyte-dependent autoimmune disease; this may be attributed to improved antioxidant defense mechanisms, blunting shifts in T-lymphocyte subset proportions and preventing DNA mutation frequencies. The beneficial effects of dietary restriction were shown in both the CD4 and CD8 T-lymphocyte subsets as well as in various immune compartments such as the spleen, mesenteric lymph nodes, peripheral blood, thymus, and salivary glands. In contrast, dietary restriction may have negative effects on macrophage function because recent evidence showed that dietary restriction rendered mice more susceptible to peritonitis and stimulated macrophages produced lower amounts of cytokines. The application of dietary restriction regimens to humans would be difficult; however, understanding the biochemical and molecular targets of dietary restriction in the immune system may lead to the development of new dietary strategies to delay or prevent the onset of aging, cancer, and autoimmune disease.

Aging↗
PubMed1994

Exercise-induced enhancement of immune function in the rat.

BACKGROUND: There have been many anecdotal reports that regular, moderate exercise confers some protective immunity against infection. There has been little scientific evidence to support this. It is also unclear whether training alters lymphocyte trafficking from the spleen to the periphery after a bout of exhaustive exercise. METHODS AND RESULTS: To determine the effect of moderate training on in vivo antibody production, using rats as an animal model, we gradually trained 18 rats using a swimming protocol for a 4-week period after injection and booster with Keyhole limpet hemocyanin antigen. There were 9 age-matched controls. At the conclusion of training, both groups underwent a short-term exhaustive swim. The trained group showed marked enhancement of IgM and IgG production. After short-term exercise, both groups had acute lymphocytosis, mainly T(suppressor)/cytolytic and natural killer cells with decreases in T(helper) (trained), B cells, and the Th-to-Ts ratio. The changes in the splenocyte subsets were the opposite of the changes in the peripheral blood. With respect to function, after exhaustive exercise, there was a slight increase in mitogenesis and interleukin-2 receptor expression to concanavalin A (untrained more than trained) compared with controls. CONCLUSIONS: Regular, moderate training enhances antibody production to specific de novo antigen both early and late. In addition, short-term exercise leads to selective release of immune cells from the spleen and results in slightly enhanced function of splenocytes. Direct stimulation by the sympathetic nervous system and catecholamines is the proposed mechanism for the changes seen after short-term exercise and possibly antibody production during training.

Animals↗
PubMed1995

Changes of some immune functions after percutaneous transluminal coronary angioplasty (PTCA).

This study aimed to evaluate some aspects of the immune response in 10 cardiopathic patients during the execution of percutaneous transluminal coronary angioplasty (PTCA) by obtaining blood samples from coronary sinus. In particular we considered some PMN functions as well as lysosomal release and oxidative metabolism evaluated as chemiluminescence and superoxide anion (O2) production. We also studied serum levels of complement C3 and C4, lymphocyte populations (CD3, CD4, CD8, CD19, CD16) and plasmatic determinations of interleukin 2 (IL2). After PTCA, we found a decrease of total count of blood lymphocytes, whereas the number of neutrophils remained unchanged. The decrease involved to a similar extent the lymphocyte subsets CD3, CD4 and CD8, whereas CD19 and CD16 were unchanged. The plasmatic levels of IL2 did not show any significant modification. Concerning PMN, their chemiluminescence was significantly increased after PTCA as compared to basal values: this response was promptly detectable in isolated PMN, both without and with stimulation with fMLP. Similarly superoxide anion production, both spontaneous and stimulated, was increased in PMN suspensions after PTCA, even if this increase did not reach statistical significance. As regards circulating levels of lysosomal enzymes, we found a significant increase of plasmatic levels of elastase, whereas the serum determinations of lysozyme and betaglucuronidase did not change. Concerning the complement system, we found a significant decrease of complement fractions C3 and C4. In conclusion, our results showed certain changes in some humoral and cellular systems; in particular the neutrophil activation through the release of proteolytic enzymes and the generation of oxygen radicals could increase the damage to vessel walls and activate other systems having a negative effect in the ischaemia-associated consequences.

Angioplasty, Balloon, Coronary↗
PubMed1988

In vitro immune functions in patients with minor, moderate, and severe kidney impairment.

We examined the in vitro immune response of lymphocytes from 86 non-dialyzed patients with progressive renal failure and 48 healthy control subjects by comparing the production of interleukin-2, the mitogen-induced proliferative response and sensitivity to glucocorticoid of lymphocyte cultures. The patients were divided in three groups with minor, moderate, and severe uremia. The uremic lymphocyte responses to stimulation with concanavalin A (Con A) were significantly lower than those of control lymphocyte cultures. A similar but not significant decrease was also seen in phytohemagglutinin (PHA) and pokeweed mitogen stimulated cultures. There was no trend towards diminishing mitogen responses with decreasing renal function. The median interleukin-2 activity in the uremic cell cultures was decreased by 50% during the culture period but the decrease was not significant. However, PHA and Con A stimulated lymphocyte cultures from all groups of patients were significantly more sensitive to the immunosuppressive effect of methylprednisolone. Thus an increased sensitivity to the immunosuppressive effect of glucocorticoid can be demonstrated in vitro at an early stage of progressive renal disease.

Adolescent↗
PubMed2004

Comparative analysis of lymphocyte activation marker expression and cytokine secretion profile in stimulated human peripheral blood mononuclear cell cultures: an in vitro model to monitor cellular immune function.

Activation of lymphocytes is a complex, yet finely regulated cascade of events that results in the expression of cytokine receptors, production and secretion of cytokines and expression of several cell surface molecules that eventually lead to divergent immune responses. Assessing the qualitative and quantitative nature of lymphocyte function following immunotherapy provides valuable information about the immune responses mediated by a therapeutic agent. To facilitate evaluation of the immunomodulatory activity of therapeutic agents, we have established a platform of in vitro immunoassays with normal human peripheral blood mononuclear cells (PBMCs) treated with several polyclonal activators that are known to exhibit different modes of action. We evaluated the kinetics of cell surface marker expression and cytokine release from PBMCs stimulated in parallel with various activating agents over a time course. These stimulating agents induced early (CD69 and CD71) and late (CD25 and HLA-DR) activation markers to varying antigen densities, indicated different cytokine profiles, and showed differential inhibition with dexamethasone (DEX), an inhibitor of early signaling events. Based on the association or correlation of the kinetics of activation marker expression and secreted cytokines, the results of our study indicate the appropriate time points for the simultaneous measurement of both these activation products. This study defines the kinetics for both measures of T cell activation and provides a comprehensive review with various polyclonal activators that can serve as a reference for monitoring lymphocyte function in clinical study samples.

Antibodies↗
PubMed1984

Immune functions in methylmalonicaciduria.

A variety of phagocytic cell and lymphocyte assays were employed to evaluate the immune status of four patients with methylmalonicaciduria . One patient had a depressed absolute granulocyte count and two patients had depressed neutrophil and monocyte chemotactic responses. All subjects had normal neutrophil phagocytic and bactericidal activities. One patient had a decreased T-cell number; blastogenic responses to phytohaemagglutinin and pokeweed mitogen were normal in all subjects. B lymphocyte measurements were variably abnormal; two children had decreased B-cell numbers; two had marginally decreased IgG levels; a third had an undetectable rubella titre; and two had elevated serum IgE concentrations. In vitro exposure of normal cells to methylmalonic acid concentrations up to 50 mg/100 ml did not affect chemotactic or lymphoproliferative responses. In conclusion, although B-cell function may be affected, no consistent abnormality of lymphocyte or phagocytic cell functions could be attributed to the metabolic disorder.

Acidosis↗
PubMed2002

Effects of delta-9-tetrahydrocannabinol on human immune function and host defense.

This review examines evidence that delta(9)-tetrahydrocannabinol (THC) can regulate and suppress human immune responses. Leukocytes express both cannabinoid receptor type 1 (CB1) and cannabinoid receptor type 2 (CB2), and levels of mRNA encoding for them are increased in peripheral blood leukocytes obtained from marijuana smokers, suggesting cannabinoid receptor activation in vivo. Exposure of human T-cells to THC suppresses their proliferation, inhibits the release of interferon-gamma, and skews the balance of T-helper cytokines towards a type 2 response. The majority of these effects are CB2 receptor-dependent. Consistent with an impact of THC on cell-mediated immunity, alveolar macrophages (AMs) recovered from the lungs of marijuana smokers are suppressed in their ability to release pro-inflammatory cytokines and nitric oxide (NO), and kill bacteria. Macrophage function is restored by treatment with interferon-gamma, a type 1 cytokine. Habitual exposure to THC appears capable of impacting on human cell-mediated immunity and host defense.

Cell Division↗
PubMed1992

Effects of cefodizime on non-specific immune functions in patients with multiple myeloma.

The effects of cefodizime (CDZ) on non-specific immunity in patients with multiple myeloma were studied in a randomized, placebo-controlled trial. A total of 51 patients with newly diagnosed multiple myeloma were admitted to the study, 27 of whom received CDZ 2 gi.v. once daily for seven days and 24 ascorbic acid 1 g daily i.v. for one week. Granulocyte chemotaxis, neutrophil biochemiluminescence and phagocytosis were determined at baseline, and at 48 h after the last dose. At baseline, chemiluminescence, phagocytosis and, to a lesser extent, granulocyte chemotaxis were diminished in both patient groups compared to healthy volunteers. After treatment, a significant increase in chemiluminescence and phagocytosis was observed in the CDZ group, while a slight increase in granulocyte chemotaxis did not reach statistical significance. No changes were observed in the control group. It is concluded that CDZ enhanced non-specific immune mechanisms in patients with multiple myeloma.

Aged↗
PubMed1991

Effects of short-term administration of human chorionic gonadotropin on immune functions in cryptorchid children.

To delineate the effects of human chorionic gonadotropin (hCG) administration on immune responsiveness, immunological parameters including serum immunoglobulins, total and differential white blood cell count T and B lymphocyte membrane phenotype, in vitro, proliferative response to phytohaemagglutinin, Concanavalin A (ConA) and pokeweed mitogen were studied in 13 prepubertal cryptorchid boys before, during, and 3 months after hCG therapy. Before treatment, all the immunological parameters were normal except for an unexpected high percentage of T suppressor-cytotoxic cells (CD8+). During therapy, the absolute number of total peripheral blood lymphocytes, and that of total T-cells, T helper-inducer cells and of CD8+ subsets were diminished. The percentage of CD8+ cells and lymphocyte response to ConA decreased significantly and returned to normal after hCG withdrawal. The possible effects of long-term hCG treatment remain to be determined.

Child↗
PubMed1999

Exercise and immune function: effect of ageing and nutrition.

Strenuous exercise is followed by lymphopenia, neutrophilia, impaired natural immunity, decreased lymphocyte proliferative responses to mitogens, a low level of secretory immunoglobulin A in saliva, but high circulating levels of pro- and anti-inflammatory cytokines. These exercise-induced immune changes may provide the physiological basis of altered resistance to infections. The mechanisms underlying exercise-induced immune changes are multifactorial and include neuroendocrinological and metabolic mechanisms. Nutritional supplementation with glutamine abolishes the exercise-induced decline in plasma glutamine, but does not influence post-exercise immune impairment. However, carbohydrate loading diminishes most exercise effects of cytokines, lymphocyte and neutrophils. The diminished neutrophilia and elastase (EC 3.4.21.37) responses to eccentric exercise in elderly subjects were enhanced to levels comparable with those of young subjects by fish oil or vitamin E supplements. However, although vitamin C supplementation may diminish the risk of contracting an infection after strenuous exercise, it is not obvious that this effect is linked to an effect of vitamin C on exercise-induced immune changes. In conclusion, it is premature to make recommendations regarding nutritional supplementation to avoid post-exercise impairment of the immune system.

Aging↗
PubMed2002

[Effect of folium ginkgo extract on the erythrocyte immunity function and serum lipid peroxide in asphyxia neonate].

OBJECTIVE: To observe the changes of erythrocyte immunity and serum lipid peroxide in asphyxia neonate, and to study the effect of Folium Ginkgo extract (FGE) on them. METHODS: Thirty asphyxia neonates were randomly divided into 2 groups, the treated group and the control group, 15 in each group. Erythrocyte C3b receptor rosette rate (E-C3bRR), erythrocyte immune complex rosette rate (E-ICR), blood superoxide dismutase (SOD) activity and serum lipid peroxide (LPO) level were determined at 24 hrs after birth. Conventional treatment was given to both groups and FGE (15 mg/kg.d) was given to the treated group additionally for 7-8 days, then the above-mentioned parameters were re-examined and neonatal behavioral neurological assessment (NBNA) was measured as well. RESULTS: E-C3bRR and SOD lowered, E-ICR and serum LPO increased in the asphyxia neonate significantly (P < 0.05). After treatment, comparison between the two groups showed that E-C3bRR and SOD were higher, E-ICR and serum LPO were lower in the treated group than those in the control group, and NBNA scoring was obviously higher in the former than that in the latter (all P < 0.05). CONCLUSION: Decrease of erythrocyte immunity in asphyxia neonate is related to the declined anti-oxidation ability and lipid peroxidase injury. FGE could suppress the free radical production, scavenge free radicals, antagonize the lipid peroxidation injury of cell membrane and up-regulate erythrocyte immunity. It displays the effects of nerve tissue protection and hypoxia-ischemic brain injury alleviation.

Asphyxia Neonatorum↗