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[Effect of fuzheng jianpi recipe on content of trace element and immune function in children with spleen deficiency anorexia].

OBJECTIVE: To evaluate the efficacy and prospect of Fuzheng Jianpi Recipe (FZJPR) in treating children's Spleen deficiency anorexia (CSDA) by means of observing its effect on trace element content and immune function. METHODS: One hundred and thirty cases of CSDA were treated with FZJPR, one dose per day in decoction, orally taken, 30 days for one therapeutic course. Levels of T-lymphocyte subsets, IL-2R, immunoglobulin and trace elements were determined before and after treatment, and compared with those in the control group consisted of 60 healthy children. RESULTS: In the treated group, abnormal figures were shown in T-lymphocyte subsets, especially in lowering of CD3 and CD4 count before treatment, and IgG content was reduced also. After treatment, CD3, CD4, CD4/CD8 ratio as well as IgG and IgA were improved significantly (P < 0.01), IL-2R percentage approached normal. Moreover, the levels of Zn and Fe changed significantly (P < 0.01). CONCLUSION: FZJPR could improve the trace elements content and immune function in CSDA children, so it is effective in treating CSDA.

Anorexia↗

Detection of the effects of repeated dose combined propoxur and heavy metal exposure by measurement of certain toxicological, haematological and immune function parameters in rats.

In the present study, an immunotoxicity test system, containing general toxicological (body weight gain, organ weights), haematological (WBC,RBC, Ht, mean cell volume of the RBCs, cell content of the femoral bone marrow), and immune function (PFC assay, DTH reaction) investigations, was used for detection the effects of a 4 weeks repeated low dose combined oral exposure of male Wistar rats with propoxur and the heavy metals arsenic or mercury. Two doses of the compounds were used: a higher one (the lowest dose which resulted in significant change of at least one parameter examined in previous dose-effect experiments), and a lower one (the highest dose which proved to be non-effective). The applied doses were: 8.51 and 0.851 mg kg(-1) of propoxur, 13.3 and 3.33 mg kg(-1) of NaAsO(2), and 3.20 and 0.40 mg kg(-1) of HgCl(2). In the combination treatment, the high dose of propoxur was combined with the low dose of arsenic or mercury, and the high doses of each heavy metals were combined with the low dose of propoxur. The main finding of this study was that some of the combinations significantly altered the relative weight of liver, adrenals and kidneys, related to both the untreated and the high dose internal control. Among the immune functions examined, only the PFC content of the spleen showed a trend of changes in certain combinations versus the corresponding high dose control. According to the present results, combined exposure with propoxur and the heavy metals examined can modify the detection limit of the single compounds and/or may alter their toxic effects.

Adrenal Glands↗

Tumor necrosis factor alpha and human immunodeficiency virus-specific functional immune responses after immunization with Gp120-depleted, inactivated HIV-1 in incomplete Freund's adjuvant (REMUNE) in HIV-1-seropositive subjects.

OBJECTIVE: We examined the relation between tumor necrosis factor-alpha (TNF-alpha) levels and human immunodeficiency virus type 1 (HIV-1)-specific functional immune responses, as measured by HIV-1 antigen-stimulated lymphocyte proliferation and beta-chemokine production after immunization with gp120-depleted, inactivated HIV-1 in incomplete Freund's adjuvant (i.e., HIV-1 Immunogen; REMUNE, The Immune Response Corporation, Carlsbad, CA, U.S.A.). STUDY DESIGN/METHODS: HIV-1-seropositive subjects who enrolled in an open-label study were immunized with REMUNE every 12 weeks and monitored for 60 weeks. HIV-1 antigen-stimulated lymphocyte proliferation and RANTES production were measured in peripheral blood mononuclear cells (PBMCs). TNF-alpha levels were measured in serum. RESULTS: TNF-alpha (P = 0.0003) significantly decreased and HIV-1 antigen-stimulated RANTES production (P = 0.002) and lymphocyte proliferation (P = 0.07) increased after immunization with REMUNE. TNF-alpha levels negatively correlated with HIV-1 antigen-stimulated RANTES production (r = -0.71; P = 0.0002) and lymphocyte proliferation (r = -0.37; P = 0.09). CONCLUSIONS: This study demonstrated decreased TNF-alpha levels with a concomitant augmentation of HIV-specific functional immunity in subjects immunized with REMUNE. Because TNF-alpha has been implicated in the induction of anergy in HIV-1 infection, the ability to decrease TNF-alpha may allow the immune system to respond to HIV and non-HIV antigens. Larger studies are being conducted to confirm the clinical utility of REMUNE in combination with potent antiviral drugs.

AIDS Vaccines↗

Effects of a Quillaja saponaria extract on growth performance and immune function of weanling pigs challenged with Salmonella typhimurium.

Ninety-six pigs (initially 8.9 kg and 24 d of age) were used in a 28-d experiment to determine the effects of Quillaja saponaria extract (QS) on weanling pig growth performance and immune function in response to enteric disease challenge with Salmonella typhimurium (ST). Experimental treatments were arranged in a 2 x 4 factorial with main effects of disease challenge (control vs ST-challenge) and dietary addition of QS (0, 125, 250, or 500 mg/kg). Pigs were fed QS diets for 14 d and then challenged orally with ST or sterile media. There were no differences in ADG or ADFI among dietary treatments, but gain/feed ratio (G/ F) was depressed (P < 0.06) in pigs fed 250 mg/kg QS. ST-challenge reduced ADG (P < 0.05), ADFI (P < 0.05), and G/F (P < 0.05) 1 wk after challenge. Daily estimates revealed reductions in feed intake in ST-infected pigs on d 2 to 5 following infection (P < 0.05), and rectal temperature was increased maximally 2 d following infection (P < 0.05). There was a marked decline in serum IGF-I during the 6 d after ST-infection (P < 0.05). ST-challenge produced a rise (P < 0.05) in serum haptoglobin on d 7 after challenge, and serum alpha1-acid glycoprotein (AGP) in ST-challenged pigs also was elevated (P < 0.05) above controls on d 7 and 14 after challenge. Serum immunoglobulin (Ig) M increased (P < 0.05) over time in both groups, and serum IgM of ST-challenged pigs was greater than controls on d 7 after challenge (P < 0.05). Serum IgG was not affected by enteric disease challenge; however, on d 7 and 14 after disease challenge, serum IgG for both groups was greater (P < 0.05) than on d 0. Dietary QS had no significant influence on any of the end points used to characterize the acute phase response to ST-challenge. Phagocytic cell function was depressed in pigs fed 250 (P < 0.05) and 500 (P < 0.05) mg/kg as compared to pigs fed 125 mg/kg QS. Yet, there was no difference in phagocytic function among pigs fed 0, 250, or 500 mg/kg QS. We conclude that this model of enteric disease invokes an acute phase response accompanied by decreases in feed intake and serum IGF-I. Furthermore, dietary QS, at the levels fed in this study, appears to offer little benefit to growth performance or immune function in the presence or absence of ST-challenge.

Acute-Phase Proteins↗

Suppressive effects of morphine pellet implants on in vivo parameters of immune function.

Chronic morphine treatment elicits a variety of immunosuppressive effects in mice. Most of the work describing this immuno-suppressive activity of the opioid is based on in vitro assessments of the performance of certain components of the immune system in morphine-treated animals. Relatively little has been done by way of tracking the effects of chronic morphine treatment on immunologic parameters in the intact animal. Therefore, this study used several classic in vivo determinations of immune function in mice treated chronically with morphine. Morphine pellet (75 mg) implantation led to a significant inhibition (91%) of paw swelling in a picryl chloride-induced delayed type hypersensitivity response. Uptake of iododeoxyuridine in an in vivo lymphocyte proliferation assay and splenomegaly in a graft vs. host reaction were also significantly suppressed by morphine pellet implantation (34 and 52%, respectively). Coimplantation of a naltrexone pellet (10 mg) completely reversed the suppressive responses to morphine in each assay. Naltrexone alone had no significant effect in any of the assays. The suppressive effects of morphine were less pronounced in adrenalectomized mice in the graft vs. host assay (51% vs. 9% reduction in morphine-pelleted shams relative to morphine-pelleted adrenalectomized mice). These findings indicate the pathophysiologic significance of the previously reported suppression of in vitro correlates of immune function in morphine-pelleted mice. The results further demonstrate that the immunosuppressive effects observed after morphine pellet implantation are naltrexone reversible and suggest that activation of the adrenal is one potential mechanism for this effect.

Animals↗

Stress, leukocyte trafficking, and the augmentation of skin immune function.

Delayed type hypersensitivity (DTH) reactions represent cell-mediated immune responses that exert important immunoprotective (resistance to viruses, bacteria, and fungi) or immunopathologic (allergic or autoimmune hypersensitivity) effects. We have used the skin DTH response as an in vivo model to study neuro-endocrine-immune interactions. 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 (e.g., wounding) that may be imposed by a stressor (e.g., an aggressor). Studies showed that acute (2 hours) stress experienced before primary or secondary cutaneous antigen exposure induces significantly enhanced skin DTH. This enhancement involves innate as well as adaptive immune mechanisms. Adrenalectomy eliminates the stress-induced enhancement of DTH. Acute administration of physiological concentrations of corticosterone and/or epinephrine to adrenalectomized animals enhances skin DTH. Compared with those in controls, DTH sites from acutely stressed or hormone-injected animals show significantly greater erythema and induration, numbers of infiltrating leukocytes, and levels of cytokine gene expression. In contrast to acute stress, chronic stress is immunosuppressive. Chronic exposure to corticosterone or acute exposure to dexamethasone significantly suppresses 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. Elucidation of mechanisms mediating a stress-induced enhancement of skin immune function is important because such immunoenhancement can have protective (wound healing, resistance to infection) or pathological (allergic or autoimmune hypersensitivity) consequences.

Animals↗

Immune function in transgenic mice overexpressing growth hormone (GH) releasing hormone, GH or GH antagonist.

Effects of life-long exposure to high levels of homologous or heterologous growth hormone (GH) and effects of GH resistance on selected parameters of immune function were studied in adult male transgenic mice overexpressing GH releasing hormone (GHRH), bovine (b) GH or an antagonistic bGH analog. In metallothionein I (MT)-bGH transgenic mice with high peripheral levels of bovine GH, there were significant increases in the absolute weight of the thymus and the spleen and in the mitogenic responses of splenocytes to concanavalin A (ConA), lipopolysaccharide (LPS) and phytohemagglutinin (PHA), as compared to age-matched normal animals. There were no significant differences between MT-bGH transgenic and normal mice in splenocyte viability or in delayed-type hypersensitivity measured by the allergic contact dermatitis response to oxazolone. Similar results, including significant stimulation of splenocyte responses to ConA, LPS, and PHA, were obtained in MT-hGHRH transgenic mice in which overexpression of GHRH leads to striking pituitary enlargement and massive elevation of peripheral levels of homologous (mouse) GH. In MT-bGH-antagonist transgenic mice in which overexpression of an antagonistic bGH analog interferes with the actions of endogenous GH, spleen weight was reduced but proliferative responses of splenocytes to ConA, LPS, and PHA were not affected. It is concluded that overexpression of heterologous or homologous GH in transgenic mice can lead to significant stimulation of some parameters of immune function, whereas antagonism of GH action by expression of an antagonistic GH analog does not affect splenocyte responses to mitogens.

Acromegaly↗

Supplementation of food with Enterococcus faecium (SF68) stimulates immune functions in young dogs.

The gut microflora play a crucial role in several physiologic functions of the host, including maturation of the gut-associated lymphoid tissues during the first months of life. Oral administration of probiotic lactic acid bacteria (LAB) modulates the immune system of humans and some laboratory animals. This effect has never been examined in dogs; therefore, our aim was to study the capacity of a probiotic LAB to stimulate immune functions in young dogs. Puppies were allotted to two groups receiving either a control diet or a diet supplemented with 5 x 10(8) colony forming units (cfu)/d of probiotic Enterococcus faecium (SF68) from weaning to 1 y of age. Fecal and blood samples were collected from the dogs at different time points for the measurement of fecal immunoglobulin (Ig)A, circulating IgG and IgA, and the proportions of lymphoid cell subsets. Fecal IgA and canine distemper virus (CDV) vaccine-specific circulating IgG and IgA were higher in the group receiving the probiotic than in controls. There were no differences in the percentages of CD4(+) and CD8(+) T cells between the groups, but the proportion of mature B cells [CD21(+)/major histocompatibility complex (MHC) class II(+)] was greater in those fed the probiotic. These data show for the first time that a dietary probiotic LAB enhance specific immune functions in young dogs, thus offering new opportunities for the utilization of probiotics in canine nutrition.

Animal Feed↗

Aging and immune function: a possible role for growth hormone.

Elderly individuals have four to five times the case rate of cancer, tuberculosis and herpes zoster and six to seven times the fatality rate from pneumonia compared to young adults. This may be causally related to two changes that occur with aging, i.e. decreased growth hormone (GH)/insulin-like growth factor-1 (IGF-1) production and decreased immune function. Data from our laboratory as well as others have shown that, based on either GH secretory dynamics or IGF-1 levels, approximately 40% of adults aged 60 and older are GH deficient. In the same population of subjects, immune function decreases such that there is a decline in cell-mediated and humoral immune responsiveness. Some of these immune deficits have been shown to be reversed in humans and primates by GH and/or IGF-1 treatment. This paper will review some of these data.

Adult↗

Adrenal steroid receptor activation in vivo and immune function.

Recent studies have indicated significant differences among immune and other tissues in in vivo adrenal steroid receptor activation after a given hormone exposure. Nevertheless, the relationship between in vivo receptor activation and functional measures of the immune response has not been determined. Type I and type II adrenal steroid receptor binding in conjunction with mitogen-induced T-cell proliferative responses were measured in the spleens of Sprague-Dawley rats that were administered various concentrations of dexamethasone (DEX). A linear relationship between type II receptor binding and splenocyte proliferation was found, with decreases in measurable type II receptors (indicating in vivo receptor activation) being highly correlated with decreases in immune function. There was no evidence of spare type II receptors. In vitro studies using the type II receptor antagonist RU 486 confirmed that the inhibitory effect of DEX on splenocyte proliferation was mediated via the type II receptor. These findings provide a foundation for future studies evaluating glucocorticoid effects on immune system function and suggest that evidence of in vivo receptor activation may be critical for predicting when and in which tissues adrenal steroid hormones may be capable of modulating the immune response.

Analysis of Variance↗

Vasoactive intestinal peptide modulates Langerhans cell immune function.

Epidermal nerves lie in close proximity to Langerhans cells (LC) and are capable of releasing peptides that modulate LC function, including calcitonin gene-related peptide and pituitary adenylate cyclase-activating polypeptide. The neuropeptide vasoactive intestinal peptide (VIP) has also been found in cutaneous nerves and mRNA, for the VIP receptor vasoactive intestinal peptide receptor type 1, and vasoactive intestinal peptide receptor type 2 have been found in murine LC and the LC-like cell line XS106. We examined the effects of VIP on LC function and cutaneous immunity. VIP inhibited elicitation of a delayed-type hypersensitivity response in previously immunized mice by epidermal cells enriched for LC content pulsed with Ag in vitro. VIP also inhibited the ability of unseparated epidermal cells to present Ag to a T cell clone and hybridoma and the ability of highly enriched LCs to present to the T cell clone. Inhibition of presentation to the hybridoma was observed with an antigenic peptide that does not require processing, suggesting that VIP is active at a step independent of Ag processing. To elucidate the mechanism(s) by which VIP may mediate these effects, we determined the effects of VIP on LC cytokine production using the XS106 cell line as a surrogate for LC. VIP augmented the production of the IL-10 in LPS-stimulated XS106 cells while down-regulating IL-12 and IL-1beta production. Thus, VIP, like pituitary adenylate cyclase-activating polypeptide and calcitonin gene-related peptide, down-regulates LC function and the associated immune response.

Animals↗

Effects of citrus fragrance on immune function and depressive states.

In our previous experiments on animals evidence was found that citrus fragrance can restore the stress-induced immunosuppression, suggesting that citrus fragrance may have an effect on restoring the homeostatic balance. Since a dysregulation of the neuroendocrine and immune function is thought to be associated with psychosomatic or psychiatric disorders an attempt was made to restore their mental health by stimulation of one of the sensory systems. Fragrance (citrus was our choice) which comforts through stimulation of the olfactory system was applied to depressive patients. It was given to 12 depressive subjects and the results indicated that the doses of antidepressants necessary for the treatment of depression could be markedly reduced. The treatment with citrus fragrance normalized neuroendocrine hormone levels and immune function and was rather more effective than antidepressants.

Adult↗

Immune functions of proteinase 3.

The primary function of neutrophil-derived serine proteases, neutrophil elastase, cathepsin G, and proteinase 3 (PR3) are thought to be the degradation of extracellular proteins at sites of inflammation, but excessive, prolonged, or inappropriate proteolytic activity causes harmful effects in the body. Although there are strong structural similarities among these proteases, PR3 has unique properties in many respects. In particular, PR3 is a major target antigen of autoantibodies, anti-neutrophil cytoplasmic antibodies (ANCA). Recent findings also revealed that PR3 is critically involved in the regulation of immune function. This review discusses the expression of PR3 in non-hemopoietic cells and focuses on the immune functions of PR3 with respect to direct modulation of cell signaling by PR3, PR3-mediated cell activation, and the possible involvement of protease-activated receptors, modulation of the cytokine network, innate immunity and PR3, and recent findings about the generation and function of ANCA.

Animals↗

Prostaglandins in experimental syphilis: treponemes stimulate adherent spleen cells to secrete prostaglandin E2, and indomethacin upregulates immune functions.

Incubation of microorganisms with macrophages enhances the production of prostaglandin E2 (PGE2). Previous research had indicated that macrophages from syphilitic rabbits suppressed spleen cell synthesis of interleukin-2 (IL-2); this suppressive activity was reversed by indomethacin. Experiments were designed to further characterize the involvement of prostaglandins in immune processing. When Treponema pallidum was incubated with unfractionated spleen preparations, PGE2 production was accelerated, and within 24 h, pharmacologic concentrations of the prostaglandin were detected. When cytochalasin B was used to block phagocytosis, decreased levels of PGE2 were apparent. Commercial preparations of PGE2, in the range generated by macrophage-treponeme interaction, inhibited concanavalin A-induced IL-2 secretion by splenic cells. T. pallidum stimulated IL-1 production by adherent cells, and indomethacin markedly enhanced this effect. In vivo, indomethacin upregulated immune function. Two groups of rabbits were infected, and one was given daily injections of indomethacin for 18 days. Both groups were treated with penicillin to terminate infections. One week later, rabbits were challenged with viable organisms to determine their immune status. The indomethacin-treated group was more resistant to reinfection. In further research, indomethacin enhanced the immunogenicity of vaccine preparations containing heat-killed T. pallidum. Results are discussed in terms of the role of PGE2 as it impinges on immune functions involving macrophage activation (IL-1 production) and T lymphocyte activation (IL-2 production).

Animals↗

Immune function in healthy inner-city children.

The importance of investigating immunity in healthy children has been underscored in the last few years by studies of the immune pathology of childhood illnesses, including human immunodeficiency virus. This study reports both ennumerative and functional immune measures in healthy inner city children. A total of 152 of 207 children studied were completely heathy at the time of venipuncture and were included in this study. Laboratory immune batteries were completed (or begun) the same day as venipuncture. Relationships between age, gender, ethnicity, and immunity were then analyzed. We found that gender predicted both the absolute number and the percentage of T cells and helper cells and the percentage of natural killer cells. Total leukocyte counts and percentages of lymphocytes and granulocytes were related to ethnicity, as was the response to mitogen stimulation (concanavalin A and pokeweed mitogen) and phagocytic ability. In conclusion, age, gender, and ethnicity factors were found to contribute to differences in various immune measures in children and require further investigation.

Child↗

[Effect of low dose rhTNF-alpha on immune function of lymphocytes in burned rats].

SD rats (200-230 g body weight) were randomly divided into three groups: (1) sham burn; (2) burn; (3) burn plus rhTNF-alpha. Third degree burn of 30% TBSA on the trunk was produced in groups 2 and 3. Intravenous rhTNF-alpha(10 micrograms/kg) was administered 6 hours postburn and once daily thereafter for 5 days in group 3. At 5 days postburn, splenic lymphocytes obtained from all the animals were used for the determination of distribution of T lymphocyte subsets with flowcytic analysis and activity of IL-2(Gills method). The results indicated that low dose rhTNF-alpha in vivo could improve distribution of splenic T lymphocyte subsets in burned rats by increasing the numbers of W3/25(Th) and decreasing the number of OX-8(Ts), and the ratio of W3/25/OX-8 was raised. In vitro the proliferation response of T lymphocytes to ConA was enhanced and the activity of IL-2 was increased by 108%, 149% and 168%, respectively, in group 3 compared with that in group 2. However, a dose-dependent effect, in that a small dose (< or = 10 ng/2.5 x 10(6) cells) of rhTNF-alpha improved the immune function of T lymphocytes, while a higher dose inhibited T lymphocyte immune function. These findings showed that rhTNF-alpha improved not only the distribution of T lymphocyte subsets but also their immune activity.

Animals↗

Severe depression of host immune functions following closed-bone fracture, soft-tissue trauma, and hemorrhagic shock.

OBJECTIVE: To determine the contribution of soft-tissue trauma plus hemorrhage, bone fracture and hemorrhage, as well as the contribution of bone fracture, soft-tissue trauma and hemorrhage on host immune function. SUBJECTS: Adult male mice (n = 6/group). DESIGN: Prospective, randomized, controlled study. SETTING: Animal laboratory at a university-affiliated hospital. INTERVENTIONS: Closed-bone fracture (right lower leg; external fixation) and/or soft-tissue trauma (2.5-cm midline laparotomy, closed in two layers) were induced before hemorrhagic shock (mean arterial blood pressure of 35 +/- 5 (SEM) mm Hg for 90 mins, followed by fluid resuscitation) in male C3H/HeN mice and the animals were killed at 72 hrs after initiation of the experiment. MEASUREMENTS AND MAIN RESULTS: Splenocyte interleukin (IL)-2 and IL-3 release capacity, as well as splenic and peritoneal macrophage IL-1 and IL-6 release capacity were determined. Different traumatic insults, i.e., bone fracture or soft-tissue trauma in conjunction with hemorrhage, produced comparable immune depression. More significant depression of splenocyte IL-2 and IL-3 release capacity as well as macrophage IL-1 and IL-6 release capacity occurred with the combined insult (i.e., bone fracture/soft-tissue injury and hemorrhage) than after bone injury or tissue trauma alone with hemorrhage. CONCLUSIONS: The combination of closed-bone fracture and soft-tissue trauma before hemorrhage leads to even more compromised immunity than either soft-tissue trauma or closed-bone fracture along with hemorrhage. The markedly depressed immune function following bone injury, soft-tissue trauma, and hemorrhagic shock may contribute to the increased susceptibility of severely injured patients to sepsis and the ensuing multiple organ failure in the clinical situation.

Animals↗

Oxidized lipid depresses canine growth, immune function, and bone formation.

Dietary oxidized lipids can increase oxidative stress and potentially contribute to a variety of disease syndromes. This research describes the first use of a canine model to assess the effects of dietary oxidized lipids on growth, antioxidant status, and some immune functions. Three groups of eight, two-month old coon-hound puppies were pair fed diets for 16 weeks. The control diet contained <50 ppm aldehydes, and two additional diets contained thermally oxidized lipids targeted to contain 100 ppm aldehydes (medium-oxidation) and 500 ppm aldehydes (high-oxidation). Dogs fed the high-oxidation diet weighed less than those from the medium-oxidation (P < 0.05) and control groups (P < 0.001) at the end of the study. Oxidized lipids reduced serum vitamin E levels, total body fat content, and bone appositional rate. At different time points of the study, peripheral blood neutrophils and monocytes from dogs fed the HO diet had reduced oxidative burst capacity and produced less superoxide and hydrogen peroxide when stimulated with phorbol esters compared to the control group. Lymphocyte blastogenesis in response to concanavalin A was suppressed by dietary oxidized lipid. This study indicates that dietary oxidized lipids negatively affect the growth, antioxidant status, and some immune functions of dogs. Importantly, some effects are evident at 100 ppm aldehydes in the diet, which is a moderate level of oxidation. The rapid growth and weight gain of the dog during the first 6 months of life may also provide a better model for assessing the risks of dietary oxidized lipid in children and adolescents than previously used rodent models.

Aldehydes↗