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Enhancement of immune function and tumor growth inhibition by antibodies against prostaglandin E2.

Mice bearing a Lewis lung carcinoma (LLC) were passively immunized against prostaglandin E2 (PGE2) by administration of rabbit serum containing anti-PGE2 antibodies. The effect of PGE2-immune serum on the suppressed immunity of LLC-bearing mice was examined. Treatment of tumor-bearing mice with anti-PGE2 prevented the suppression of lymphocyte mitogenesis and the alterations in macrophage migration which typically occur in LLC-bearing mice. Furthermore, tumor growth was reduced in LLC-bearing mice which received antibodies directed against PGE2 rather than a placebo treatment.

Animals↗

[Effects of autologous hematopoietic stem cell transplantation on immune function in patient with systemic lupus erythematosus].

To investigate the effects of autologous hematopoietic stem cell transplantation (AHSCT) on immune index in patient with systemic lupus erythematosus (SLE), and evaluate its treatment outcome, the flow cytometry (FCM) and enzyme linked immunosorbent assay (ELISA) were used to detect the leukocyte differentiation antigen, sIL-2R, IL-6, C3, C4, autoantibodies, immunoglobulin for 33 case of SLE before transplantation and at 1, 3, 6, 12 months after transplantation. The results showed that the ratio of CD4(+), CD19(+) cell, the level of sIL-2R, IL-6 and the positive rate of autoantibodies were significantly lower, CD8(+), CD16(+)CD56(+) cell and C3, C4 were higher than those before transplantation. Out of the 33 patients, 26 achieved CR, 3 reached PR and 4 relapsed at 4 - 6 months after transplantation. It is concluded that the immune indexes of patients with SLE changed significantly following AHSCT. These immune indexes may be indications to predict the status of remission in patient with SLE.

Adolescent↗

Effect of alpha-interferons on immune function.

alpha-Interferons (IFN-alphas) have been shown to have pleiotropic effects on most components of the immune system. The most studied effect of IFN-alphas on the immune system is their ability to augment natural killer cell activity, an effect that is mediated by a complex variety of mechanisms. Both naturally occurring and recombinant IFN-alphas have shown differences of as much as 100-fold in their ability to activate natural killer activity. Although consensus IFN, a synthetic, nonnaturally occurring hybrid IFN, has been reported to have a high natural killer stimulatory capacity relative to its antiviral activity, the available data and experimental design do not permit a definitive conclusion. In summary, it is clear that the complex immunomodulatory effects of IFN-alphas are likely to contribute to their therapeutic activity.

Antibody Formation↗

Differential activation of cell-mediated immune functions by encapsulated and surface-linked liposomal antigens.

Liposomes act as powerful adjuvants if physically associated with a protein antigen. Their effect on the immune response, however, varies with the nature of this linkage, surface-linked and encapsulated antigens having different properties. Cytometric analysis and cytokine measurements indicate that this difference may be due to the differential activation of T lymphocyte populations. Surface-linked antigen appears to preferentially stimulate CD4+ T cells to proliferate and mature into a typical Th1 phenotype; this is indicated by a positive shift in the CD4+/CD8+ ratio of sensitized splenocytes, a massive production of interferon-gamma, and the absence of interleukin-4 secretion. In contrast, encapsulated antigen, while stimulating spleen cell proliferation, does not significantly affect the CD4+/CD8+ ratio and induces only low levels of interferon-gamma production in the absence of interleukin-4 secretion. These results suggest that CD4+ and CD8+ populations are both expanded in response to encapsulated antigen but that neither typical Th1 nor Th2 phenotypes are induced. High-resolution immunocytochemical investigations show that this differential activation of T cell populations may be related to a different intracellular trafficking of antigens into professional antigen-presenting cells. Whereas surface-linked antigen remains predominantly in endosomal compartments where it may be associated with major histocompatibility (MHC) class II products for presentation to CD4+ T cells, encapsulated antigen escapes into the cytosol, reaching the MHC class I pathway for presentation to CD8+ T cells. The results therefore suggest that both liposomal antigens stimulate cell-mediated immunity albeit differently. This behavioral difference may be of practical importance in the design of adjuvants for the preferential potentiation of specific cytotoxic effector functions.

Adjuvants, Immunologic↗

[The characteristics of the development of the immune function in the transplanted spleen of newborn mouse pups in recipients of different ages. 2. The effect of the thymus on the functional development of the transplant].

The effect of the neonatal thymus grafting or "Thymostimulin" administration on the cellularity, cell composition, immune, response to SRBC and proliferative activity of T- and B-cells in vitro were determined in neonatal spleen grafted CBA/Ca female mice of different ages. Analysis of the thymus graft effect on the T- and B-cells content in the spleen transplant from the adult and old recipients demonstrated no differences. The neonatal thymus grafting led to the essential increase of the immune response, spleen cellularity and to the diametrically opposed changing from negative to positive of the sign of the correlation coefficient between the T-cells content and the cellularity of the neonatal spleen in the old recipients. The similar effect of the neonatal thymus grafting was revealed in respect of correlative connection between content of the T-cells and PFCs in spleen grafted to the old recipients too. The "Thymostimulin" injection led only to the increase of the spleen transplant cellularity. These results suggests that the young thymic microenvironment is essential for the normal T-cells differentiation and for its normal function in the neonatal spleen transplant.

Adjuvants, Immunologic↗

[Effect of intravascular laser irradiation of blood and traditional Chinese medical therapy on immune function in senile cerebral infarction patients of kidney deficiency type].

OBJECTIVE: To observe the effect of intravascular laser irradiation of blood (ILIB) therapy on cellular immunity, change of T-lymphocyte subsets and humoral immunity in senile cerebral infarction patients of Kidney deficiency type. METHODS: Seventy-five patients were divided randomly into the ILIB group and the control group treated by conventional medicine (CM). Serum CD3, CD4, CD8, IgG, IgA, IgM, C3 and C4 levels of patients were determined before and after treatment for self-control and comparing between various groups and that of normal control. RESULTS: Before treatment, in patients of both groups, the levels of CD3, CD4, CD4/CD8, C3 were all lower than normal levels significantly, C4 and IgM higher than normal (P < 0.05, P < 0.01), the level of IgG lowered in patients inclined to Kidney-Yang deficiency and raised in those inclined to Kidney-Yin deficiency (P < 0.01). After treatment, in the ILIB group, CD3, CD4 and CD4/CD8 raised significantly (P < 0.05, P < 0.01), IgG and C3 varied towards normal control (P < 0.01, P < 0.05), and C4 lowered but without significance. In the control group, the indexes changed also toward normal but without significance except the change of IgG (P < 0.05). As for IgA and IgM, marked changes were not found in both groups in comparison between before and after treatment. CONCLUSION: ILIB therapy could bi-directionally regulate cellular and humoral immunity in senile cerebral infarction patients of Kidney deficiency type, which was similar to the function in supplementing Qi and invigorating Kidney of Chinese herbal medicine.

Aged↗

HIV-1 viral protein R compromises cellular immune function in vivo.

HIV-1 viral protein R (Vpr) is a virion-associated gene product that profoundly affects T cell proliferation, induces apoptosis and can affect cytokine production in part through interfering with NF-kappa B-mediated transcription from host cells. Collectively, these effects support that Vpr could influence immune activation in vivo. However, this effect of Vpr has not been explored previously. Here we examined the effect of Vpr expression in an in vivo model system on the induction of antigen-specific immune responses using a DNA vaccine model. Vpr co-vaccination significantly altered the immune response to co-delivered antigen. Specifically, in the presence of Vpr, inflammation was markedly reduced compared to antigen alone. Vpr reduced antigen-specific CD8-mediated cytotoxic T lymphocyte activity and suppressed T(h)1 immune responses in vivo as evidenced by lower levels of IFN-gamma. In the presence of Vpr, there is a profound shift in isotype towards a T(h)2 response as determined by the IgG2a:IgG1 ratio. The data support that Vpr compromises antigen-specific immune responses and ultimately effector cell function, thus confirming a strong selective advantage to the virus at the expense of the host.

AIDS Vaccines↗

NF-kappaB family of transcription factors: central regulators of innate and adaptive immune functions.

Transcription factors of the Rel/NF-kappaB family are activated in response to signals that lead to cell growth, differentiation, and apoptosis, and these proteins are critical elements involved in the regulation of immune responses. The conservation of this family of transcription factors in many phyla and their association with antimicrobial responses indicate their central role in the regulation of innate immunity. This is illustrated by the association of homologues of NF-kappaB, and their regulatory proteins, with resistance to infection in insects and plants (M. S. Dushay, B. Asling, and D. Hultmark, Proc. Natl. Acad. Sci. USA 93:10343-10347, 1996; D. Hultmark, Trends Genet. 9:178-183, 1993; J. Ryals et al., Plant Cell 9:425-439, 1997). The aim of this review is to provide a background on the biology of NF-kappaB and to highlight areas of the innate and adaptive immune response in which these transcription factors have a key regulatory function and to review what is currently known about their roles in resistance to infection, the host-pathogen interaction, and development of human disease.

Animals↗

The effects of an arginine-free enteral diet on wound healing and immune function in the postsurgical rat.

Critically ill patients have increased rates of sepsis partly due to a down-regulated immune system. Nutrients may modulate the immune system. The following studies were performed to determine whether arginine is one of these "essential" nutrients for the immune system. Thirty-two male Sprague-Dawley rats (weighing 175 g) were divided into two groups that were pair-fed with either an elemental, arginine-supplemented enteral diet, or the same diet with arginine removed and replaced with glycine. Both diets were isocaloric, isoosmolar, and isonitrogenous. After 6 days on the diet, animals underwent testing. There were no significant differences between the arginine-supplemented and the arginine-free diet groups in blood glucose or hematocrit. The arginine-supplemented animals had higher serum albumin (4.1 +/- 0.1 mg/dL v 3.6 +/- 0.1 mg/dL; P = .035) and serum protein levels (5.2 +/- 0.1 mg/dL v 4.3 +/- 0.1 mg/dL; P = .041); and had higher thymus gland (0.53 +/- 0.03 g v 0.44 +/- 0.02 g; P less than .0001) and spleen weights (0.66 +/- 0.01 g v 0.57 +/- 0.01 g; P less than .01). Daily total urinary nitrogen excretion, nitrogen balance, and weight gain showed a tendency for the arginine-supplemented animals to retain more of their nitrogen calories. There was no difference in the amount of hydroxyproline (OHP) found in the wound cylinders of either group (both 25.6 micrograms OHP/cm polytetrafluoroethylene) but the arginine-supplemented group's wounds had greater wound bursting strengths (429 +/- 3 g/cm v 350 +/- 7 g/cm; P = .044).(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

Vitamin E status and immune function.

Evidence from animal and human studies indicates that vitamin E plays an important role in the maintenance of the immune system. Even a marginal vitamin E deficiency impairs the immune response, while supplementation with higher than recommended dietary levels of vitamin E enhances humoral and cell-mediated immunity. The current RDA level of vitamin E prevents clinical deficiency syndrome but in some situations, especially in older subjects or in a disease state, fails to maintain optimal host defense. The immunological parameters reviewed are all sensitive to changes in the availability of vitamin E and, therefore, may reflect the vitamin E status of a given individual more accurately than conventional methods.

Animals↗

Biphasic in vivo immune function after low- versus high-dose alcohol consumption.

A series of experiments was performed to assess the alterations in immune status in vivo that are associated with differences in the amount and duration of ethanol intake. Using a nonspecific delayed cutaneous hypersensitivity-like response to the intradermal injection of phytohemagglutinin, the area of induration (skin test response) was significantly enhanced (p = 0.008) after low-dose ethanol (0.5 g/kg) administered daily by gastric gavage for 5 days. High-dose ethanol (6.0 g/kg) significantly diminished this response (p = 0.03). Using an experimental model of Mycobacterium bovis hepatitis, the host immune response was also altered in a biphasic manner after chronic, 28-day ethanol consumption. With this model 0.43 +/- 0.03 g/kg/day (mean +/- SEM) of ethanol (low dose) was associated with a 40% improvement in the removal of the organisms from liver tissue (p = 0.002). High dose (12.1 +/- 0.5 g/kg/day) impaired removal, resulting in a 55% increase in the number of viable organisms (p = 0.001). The levels of three cytokines, MIF, TNF-alpha, and IL-2, known to be involved in the modulation of the host response to mycobacterial infections, were measured in sera after the infection. The serum levels of these cytokines in response to infection did not correlate with this biphasic response to different alcohol dose levels.

Animals↗

Stress-induced augmentation of immune function--the role of stress hormones, leukocyte trafficking, and cytokines.

Delayed-type hypersensitivity (DTH) reactions represent cell-mediated immune responses that exert important immunoprotective (resistance to viruses, bacteria, and fungi) or immunopathological (allergic or autoimmune hypersensitivity) effects. We initially utilized the skin DTH response as an experimental in vivo model to study neuro-endocrine-immune interactions in rodents. We hypothesized that just as an acute stress response prepares the cardiovascular and musculoskeletal systems for fight or flight, it may also prepare the immune system for challenges which may be imposed by a stressor. The skin DTH model allowed us to examine the effects of stress at the time of primary and secondary exposure to antigen. Studies showed that acute (2h) stress experienced before primary or secondary antigen exposure induces a significant enhancement of skin DTH. Importantly, this enhancement involved innate as well as adaptive immune mechanisms. Adrenalectomy eliminated the stress-induced enhancement of DTH. Acute administration of physiological (stress) concentrations of corticosterone and/or epinephrine to adrenalectomized animals enhanced skin DTH. Compared with controls, DTH sites from acutely stressed or hormone-injected animals showed significantly greater erythema and induration, numbers of infiltrating leukocytes, and levels of cytokine gene expression. In contrast to acute stress, chronic stress was immunosuppressive. Chronic exposure to corticosterone, or acute exposure to dexamethasone significantly suppressed skin DTH. These results suggest that during acute stress, endogenous stress hormones enhance skin immunity by increasing leukocyte trafficking and cytokine gene expression at the site of antigen entry. While these results are discussed from a mechanistic and clinical relevance perspective, it is acknowledged that much work remains to be done to elucidate the precise mechanisms mediating these bi-directional effects of stress and stress hormones and their clinical ramifications.

Animals↗

[Opioid receptor mediated modulation of intrahippocampal enkephalin induced cellular immune function].

In the present work, the effect of intrahippocampal microinjection of opioid receptor antagonist naloxone on the enhancement of cellular immune responses induced by enkephalin was studied in rat. The results showed that (1) the proliferation activity of splenic lymphocytes stimulated by Con A and natural killer (NK) cell activity were decreased with microinjection of 1 microl lipopolysaccharide (LPS,50 ng/microl) into bilateral hippocampus; (2) the decrease of cellular immune responses induced by LPS could be inhibited by a preceding intrahippocampal injection of 1 microl met-enkephalin (10 microg/1 microl); (3) the enhancement of cellular immune responses induced by met-enkephalin could be blocked by an opioid receptor antagonist naloxon (10 microg/microl); and (4) cellular immune responses were also inhibited when naloxon was injected intrahippocampally alone. The above results suggest that the enhancement of cellular immune responses induced by enkephalin was mediated by opioid receptors in hippocampus.

Animals↗

[The regulation effects of Angelica sinensis on the erythrocytic immune function and IL-2 in mice].

The effects of Angelica sinensis solube extract on erythrocytic C3b receptor rosette rate and immune complex rosette rate and activities of interleukine-2 (IL-2) in mice are observed in this article. Angelica sinensis can significantly enhances erythrocytic C3b recepor rosette rate and IL-2 activities. The regulating actions of Angelica sinensis on erythrocytic C3b recepor rosette rate and IL-2 activities may be the direct effects.

Adjuvants, Immunologic↗

Exercise capacity and immune function in male and female patients with chronic fatigue syndrome (CFS).

Hyperactivition of an unwanted cellular cascade by the immune-related protein RNase L has been linked to reduced exercise capacity in persons with chronic fatigue syndrome (CFS). This investigation compares exercise capacities of CFS patients with deregulation of the RNase L pathway and CFS patients with normal regulation, while controlling for potentially confounding gender effects. Thirty-five male and seventy-one female CFS patients performed graded exercise tests to voluntary exhaustion. Measures of peak VO2, peak heart rate, body mass index, perceived exertion, and respiratory quotient were entered into a two-way factorial analysis with gender and immune status as independent variables. A significant multivariate main effect was found for immune status (p < 0.01), with no gender effect or interaction. Follow-up analyses identified VO2(peak) as contributing most to the difference. These results implicate abnormal immune activity in the pathology of exercise intolerance in CFS and are consistent with a channelopathy involving oxidative stress and nitric oxide-related toxicity.

Adult↗

Immune functions in crustaceans: lessons from flies.

In recent years insects, notably Drosophila, have emerged as a popular model for studying immune responses to bacterial and fungal pathogens. Due to the availability of the complete genome sequence, genome-wide scans of immune responses have been performed using microarray analyses. These analyses have revealed the presence of two major pathways: Toll and Imd. Each pathway consists of four steps: (i) recognition through pattern recognition receptors; (ii) modulation by serine proteases; (iii) signal transduction leading to translocation of transcription factors and (iv) humoral and cellular responses. We have compared the information from insects with those currently available in crustaceans, and have identified commonalities and differences. Remarkably, in both insects and crustaceans, little is known about their anti-viral responses. Future research will have to focus on these anti-viral immune responses ultimately to control viral diseases, which are at present a major threat to culturing penaeid shrimp.

Animals↗

A defect in cell-mediated immune function in insulin-resistant diabetic and obese subjects.

In this study, we have evaluated one aspect of the cellular immune process--in vitro release of MIF by lymphocytes obtained from controls; well-controlled, ketosis-prone, insulin-dependent diabetic patients; nonketotic diabetic patients; and nonhyperglycemic obese patients. The results showed that MIF release by cells from well-controlled, insulin-dependent diabetic, nonketotic diabetic, and nonhyperglycemic obese subjects was 100% +/- 8, 48% +/- 17, and 36% +/- 17 of control values, respectively. Thus insulin-sensitive, ketosis-prone diabetic patients have normal MIf release while well-controlled on insulin therapy, whereas insulin-resistant, nonketotic diabetic and nonhyperglycemic obese patients have impaired MIF release. It is possible that this in vitro defect in a cellular immune process is related to the insulin-resistant state and that it may play a role in enhanced susceptibility to infection in insulin-resistant diabetic patients.

Adult↗