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PubMed2006

An update on parenteral lipids and immune function: only smoke, or is there any fire?

PURPOSE OF REVIEW: This paper synthesizes information from recent studies on the modulation of immune responses by lipid emulsions that are applied as part of parenteral nutrition. This issue is especially relevant in light of the high rate of infectious complications and disturbed inflammatory responses in patients receiving this form of nutritional support. RECENT FINDINGS: Studies reporting on novel emulsions based on olive and fish oils, structured lipids or mixed-type emulsions in which various lipid species replace conventional long-chain triglycerides indicate that these lipids are generally well tolerated. While long-chain triglycerides may promote inflammation due to conversion of n-6 polyunsaturated fatty acids into arachidonic acid-derived eicosanoids, structured lipids and olive oil emulsions appear more immune-neutral. Leukocyte-activating effects of medium-chain triglycerides in experimental studies await further characterization in vivo. A body of evidence shows that immune modulation by fish oil emulsions is essentially anti-inflammatory in nature. This is in line with the observation that n-3 polyunsaturated fatty acids in fish oil replace arachidonic acid in cell membranes as an eicosanoid substrate, resulting in a decreased production of pro-inflammatory mediators. Importantly, recent investigations indicate beneficial effects of parenteral fish oil on relevant clinical outcome measures. SUMMARY: The characteristics of, and mechanisms behind, the effects of various parenteral lipids on immune function are becoming increasingly well understood. The practical relevance of many of these findings is not immediately clear, however, and will have to be substantiated in adequately powered trials before we can translate these findings into a tailored approach for specific clinical situations.

Cytokines↗
PubMed2002

[Effect of the stem and leaf of Tripterygium wilfordii on immune function].

OBJECTIVE: To study the effect of water extracts from the stem and leaf of Tripterygium wilfordii Hook. f. on Hook. f. immune function. METHODS: The effect of the stem and leaf of Trpterygium wilfordii on the clearance of charcoal particles, the index of thymus gland and spleen, the level of serum hemolysin and the delayed hypersensitivity were observed in mice by ig. RESULTS: The stem and leaf of Tripterygium wilfordi could decrease the clearance of charcoal particles, the index of thymus gland and spleen, the level of serum hemolysin and inhibit the delayed hypersensitivity in mice. CONCLUSION: The stem and leaf of Tripterygium wilfordii could inhibit nonspecific, humeral and cellular immunity.

Animals↗
PubMed1995

Selective modulation of immune function resulting from in vitro exposure to methylenedioxymethamphetamine (Ecstasy).

Abuse of illicit analogs of methamphetamine (i.e., 'designer drugs') represents a growing problem. One of the most popular methamphetamine analogs is (+/-)-3,4-methylenedioxymethamphetamine (MDMA), commonly known as Ecstasy. The authors demonstrated previously that in vitro exposure to methamphetamine results in modulation of immune functional parameters necessary for host defense. The current study was performed to assess the potential direct (in vitro) immunomodulatory effect of exposure to a modified methamphetamine. Splenocytes or peritoneal macrophages from B6C3F1 mice were cultured in vitro at MDMA concentrations of 0.0001-100 microM. T-cell regulatory function was assessed by anti-CD3-mediated production of IL-2 and IL-4, B-cell function was assessed by quantitating cellular proliferation, natural immunity was assessed by quantitating natural killer (NK) cell activity, T-cell effector function was evaluated as a function of cytotoxic T-lymphocyte (CTL) activity, and macrophage function was assessed by IL-6 tumor necrosis factor (TNF) production. In vitro exposure to MDMA had no effect on B-cell proliferation at any concentration tested. In comparison, in the absence of direct cellular toxicity, production of IL-2 was enhanced at concentrations as low as 0.0001 microM. IL-4 production was not affected by exposure to any concentration of MDMA examined, suggesting a differential alteration in T-helper cell function by this compound. Basal and augmented NK cell function were enhanced at MDMA concentrations between 0.0001 and 1.0 microM when examined at an effector:target ratio of 100:1. CTL induction was significantly suppressed at a concentration of 100 microM. Finally, macrophage production of TNF was slightly suppressed at 10 and 100 microM MDMA, although this inhibition was not statistically significant.

Adjuvants, Immunologic↗
PubMed1986

Effect of transfusion on immune function in a traumatized animal model.

Blood transfusions repeatedly have been shown to prolong allograft survival, probably by stimulating suppressor T lymphocytes. The effects of transfusions on immune function in traumatized patients has not previously been investigated. We investigated the effects of transfusions on the immune system using a burned rat model. The transfusions were found to have no effect on the white blood cell counts, differential cell count, or neutrophil migration and bactericidal index. Those animals that received transfusion did exhibit impaired cell-mediated immunity and macrophage migration. Blood transfusions seem to increase further the immunosuppression seen with trauma and surgery.

Animals↗
PubMed1997

Impact of dietary yogurt on immune function.

Studies of the effects of yogurt on immunity and atopic diseases have suggested improvements in cytokine (interleukin-2 and interferon-gamma) responses and clinical scores in patients with allergic rhinitis. This study compares prospectively immune parameters of participants who received 16 oz of yogurt versus 16 oz of milk/day in a randomized cross-over design. Yogurt that contained live, active Lactobacillus bulgaricus and Streptococcus thermophilus or 2% milk was consumed for one month each. Twenty otherwise healthy adults with atopic histories documented by skin testing were enrolled. Immune studies were performed at the beginning and end of the two 1-month study phases, separated by a 2-week washout period. These studies included measurements of cellular, humoral, and phagocytic function. No adverse events were noted in either group. No significant improvements in any immune parameter were noted. The consumption of yogurt that contained the live active bacteria L bulgaricus and S thermophilus does not appear to enhance immune function in atopic individuals at the dosage and duration used in this study.

Adult↗
PubMed1991

Effects of long-term, low-dose growth hormone therapy on immune function and life expectancy of mice.

We have studied effects of long-term, low-dose growth hormone therapy on the immune function and life expectancy of Balb/c mice. Sixty male Balb/c mice were aged up to the time when they started showing signs of senescence and causal death (deaths started when they became 17 months old). The aged mice were divided into two groups of 26 mice each. One group received growth hormone (30 micrograms/mouse) subcutaneously twice a week for 13 weeks. The control group received an equal volume of saline for the same period. During this treatment period, 16 control mice died (61%) whereas only 2 of the hormone-treated mice died (7%). Four mice from each group were killed and immunological functions of splenocytes were evaluated. Hormone-treated mice had higher stimulation indices for pokeweed mitogen but not for Concanavalin-A. Total IgG production was decreased but IL-1, IL-2 and TNF production was increased. After a lag period of 4 weeks, growth hormone therapy was continued for another 6 weeks. One of the growth hormone treated mice died while the control group no longer existed. Splenocyte functions of the growth hormone treated mice were compared to those of young mice. The results showed no significant difference between cytokine production (IL-1, IL-2, TNF and IgG) in the young and the hormone treated groups. Stimulation induced by concanavalin-A and pokeweed mitogen however, was higher in the young group than the old group. The mortality curve obtained suggests that long-term low-dose growth hormone treatment prolongs life expectancy.

Aging↗
PubMed1971

Immune function in multiple myeloma: impaired responsiveness to keyhole limpet hemocyanin.

Twenty-three patients with multiple myeloma, four patients with treated localized plasmacytoma and 14 normal subjects were immunized with keyhole limpet hemocyanin (KLH). When compared to the normal subjects, the myeloma patients showed a prolonged induction time for IgM antibody formation, a more rapid switch from IgM to IgG production and a decline in the titre of total antibody produced. In vitro lymphocyte responses to KLH following immunization were reduced in the myeloma group and tended to decline with time in a manner similar to the serum antibody concentration. Most of the myeloma patients tested developed delayed hypersensitivity skin reactions to KLH, but these reactions were smaller than those of the control subjects. The patients with myeloma had also reduced in vitro lymphocyte responses to streptolysin-O and vaccinia. Immune function of the plasmacytoma patients was similar to that of the control subjects.Both humoral and cellular immunity in response to a newly encountered antigen, KLH, is impaired in patients with multiple myeloma.

Adult↗
PubMed2001

Social stress in laboratory rats: behavior, immune function, and tumor metastasis.

This report summarizes data from social confrontations studies in laboratory rats dealing with the effects of psychosocial stress on immune functioning and tumor metastasis. The paper focuses on the physiological alterations observed in subdominant males after 2 days of continuous social confrontation. A significant loss of body mass and elevated plasma concentrations of adrenal hormones in subdominant males indicate a stressful social environment. Subdominant males showed lower numbers of blood CD4 and CD8 T cells as well as reduced activity levels of T cells and natural killer (NK) cells relative to control subjects. In order to evaluate the possible health impact of suppressed NK functioning, we used the MADB 106 tumor model. A 10-fold lower tumor clearance in subdominant males demonstrates suppression of the animals' capacity to prevent metastatic development. The relationship between individual behavior and immunological outcome is briefly discussed. Together, the study of male rats in social confrontations appears to be a good model to investigate stress-induced immune modulation and tumor metastasis under relatively naturalistic social conditions.

Animals↗
PubMed1996

Envelope glycoproteins of human immunodeficiency virus type 1: profound influences on immune functions.

Infection by human immunodeficiency virus type 1 (HIV-1) leads to progressive destruction of the CD4+ T-cell subset, resulting in immune deficiency and AIDS. The specific binding of the viral external envelope glycoprotein of HIV-1, gp120, to the CD4 molecules initiates viral entry. In the past few years, several studies have indicated that the interaction of HIV-1 envelope glycoprotein with cells and molecules of the immune system leads to pleiotropic biological effects on immune functions, which include effects on differentiation of CD34+ lymphoid progenitor cells and thymocytes, aberrant activation and cytokine secretion patterns of mature T cells, induction of apoptosis, B-cell hyperactivity, inhibition of T-cell dependent B-cell differentiation, modulation of macrophage functions, interactions with components of complement, and effects on neuronal cells. The amino acid sequence homologies of the envelope glycoproteins with several cellular proteins have suggested that molecular mimicry may play a role in the pathogenesis of the disease. This review summarizes work done by several investigators demonstrating the profound biological effects of envelope glycoproteins of HIV-1 on immune system cells. Extensive studies have also been done on interactions of the viral envelope proteins with components of the immune system which may be important for eliciting a "protective immune response." Understanding the influences of HIV-1 envelope glycoproteins on the immune system may provide valuable insights into HIV-1 disease pathogenesis and carries implications for the trials of HIV-1 envelope protein vaccines and immunotherapeutics.

AIDS Vaccines↗
PubMed2005

Alterations of intestinal immune function and regulatory effects of L-arginine in experimental severe acute pancreatitis rats.

AIM: To discuss the changes of intestinal mucosal immune function in rats with experimental severe acute pancreatitis (SAP) and the regulatory effect of L-arginine. METHODS: Male adult Wistar rats were randomly divided into pancreatitis group, sham-operation group, and L-arginine treatment group. Animals were killed at 24, 48, and 72 h after SAP models were developed and specimens were harvested. Endotoxin concentration in portal vein was determined by limulus endotoxin analysis kit. CD3+, CD4+, CD8+ T lymphocytes in intestinal mucosal lamina propria were examined by immunohistochemistry. Secretory immunoglobulin A (SIgA) in cecum feces was examined by radioimmunoassay. RESULTS: Compared to the control group, plasma endotoxin concentration in the portal vein increased, percentage of CD3+ and CD4+ T lymphocyte subsets in the end of intestinal mucosal lamina propria reduced significantly, CD4+/CD8+ ratio decreased, and SIgA concentrations in cecum feces reduced at 24, 48, and 72 h after SAP developed. Compared to SAP group, the L-arginine treatment group had a lower level of plasma endotoxin concentration in the portal vein, a higher CD3+ and CD4+ T lymphocyte percentage in the end of intestinal mucosal lamina propria, an increased ratio of CD4+/CD8+ and a higher SIgA concentration in cecum feces. CONCLUSION: Intestinal immune suppression occurs in the early stage of SAP rats, which may be the main reason for bacterial and endotoxin translocation. L-arginine can improve the intestinal immunity and reduce bacterial and endotoxin translocation in SAP rats.

Acute Disease↗
PubMed1991

Studies of immunological function in mice with defective androgen action. Distinction between alterations in immune function due to hormonal insensitivity and alterations due to other genetic factors.

The presence of androgen receptors in thymocytes and the well-described effects of exogenous androgens on thymus size suggest a role for androgenic hormones in thymocyte growth and maturation. Testicular feminization (Tfm/Y) mice which bear a heritable defect in the androgen receptor protein were studied to investigate how androgens might influence immune phenotype and function. These mice were compared to two types of controls; their Tabby/Y normal male littermates and male mice of the C57 Bl/6 strain from which the Tabby and Tfm mice were derived. Thymuses and spleens from Tfm/Y mice were larger than both types of controls. Phenotypic differences in thymocyte and splenocyte subpopulations identified by the T-cell markers CD3, CD4 and CD8 suggested that T-cell maturation was altered in the androgen-resistant animal. However, both Ta/Y and Tfm/Y were found to be high producers of interleukin-4 (IL-4) by both spleen and thymus cells, while cells from the C57 mice produced predominantly IL-2. These findings suggest that some immunological features of the Tfm/Y mouse may be related to its defect in androgen action, but that high levels of IL-4 production are probably related to other genetic changes in the C57 background.

Androgens↗
PubMed2001

Effects of age and recombinant equine somatotropin (eST) administration on immune function in female horses.

Aging has been associated with declines in somatotropin and IGF-I levels as well as declines in immune function. To determine the effects of age and whether ST administration could reverse immunosenescence in horses, eight young and eight aged female standardbred horses were given 10 mg/d recombinant equine somatotropin (eST) or vehicle buffer for 49 d. Plasma IGF-I concentrations in both age groups were higher in eST-treated animals (P < 0.001), and higher in young eST-treated mares than in aged eST-treated mares during wk 4 to 7 (P < 0.001). There was a trend toward lower monocyte and granulocyte numbers (P = 0.07) in mares treated with eST. Aged mares treated with eST had lower lymphocyte numbers (P < 0.005). The percentage of CD4+ lymphocytes was higher in aged mares (P < 0.001), and the percentage of CD8+ lymphocytes was higher in young mares (P < 0.01). Lymphocyte proliferation in response to concanavalin A, phytohemagglutinin, and pokeweed mitogen was not lower in aged mares (P = 0.17, 0.17, and 0.13 respectively). Aged mares treated with eST showed a lower peak primary antibody response to keyhole limpet hemocyanin (P < 0.05). Young mares treated with eST showed a higher peak primary antibody response to keyhole limpet hemocyanin (P < 0.05). Like other species, horses exhibit similar signs of age-related declines in various immune parameters, but those of aging were not reversed with eST treatment.

Aging↗
PubMed1998

Alterations of immune functions in heroin addicts and heroin withdrawal subjects.

Conflicting results, both decreased and increased, have been reported concerning the function of T-lymphocytes in heroin addicts. We investigated the alterations of T-lymphocyte proliferative responses and immunophenotypic markers on lymphoid cells in heroin addicts and during different periods of heroin withdrawal in addicted subjects. This study has demonstrated a decrease in the response of T-lymphocytes to 1.2, 2.5, 5 and 10 microg/ml of phytohemagglutinin stimuli in heroin addicts and 1- to 5-day heroin withdrawal subjects compared with controls. Similarly, in an in vitro study, 10(-4), 10(-6) and 10(-8) M concentrations of morphine were shown to suppress 0.6 and 2.5 microg/ml of PHA-stimulated T-lymphocyte obtained from naive subjects. This inhibitory effect of morphine on PHA stimulation was completely abolished by 100 microM naloxone. The immunological parameters of total T-lymphocytes (CD3), T-helper cells (CD4), cytotoxic T-cells (CD8), B-cells and natural killer cells that are the immunophenotypic markers studied by flow cytometric analysis were altered in heroin addicts, 15- to 21-day and 6- to 24-month heroin withdrawal subjects, when compared with controls. These results suggest that heroin addicts and short period (15 to 21 days and 6 to 24 months) of heroin withdrawal have decreases in their immune system functioning and that the heroin withdrawal subjects seem to gradually reverse their immunological parameters to normal levels when withdrawal was sustained >/=2 years. This is the first report examining immune function in heroin withdrawal subjects using the "cold turkey" method. The results are beneficial for further study of the mechanism responsible for the opioid-induced changes in immune function.

Adult↗
PubMed2005

[Effects of ethyl pyruvate on cell-mediated immune function in rats with delayed resuscitation after burn injury].

OBJECTIVE: To investigate the effects of ethyl pyruvate (EP) on cell-mediated immune function in rats with delayed resuscitation after burn injury, and its potential regulatory mechanism. METHODS: Wistar rats were subjected to 30% full-thickness scald injury with delayed resuscitation. One hundred and three male rats were randomly divided into normal controls (n=7), sham scald group (n=32), scald group (n=32) in which 40 ml/kg normal saline was infused peritoneally 6 hours after scald, and EP treatment group (n=32) in which 40 mg/kg EP was injected peritoneally 6 hours after scald. Animals were sacrificed on postburn day 1, 3, 5, and 7, and spleen was collected to determine splenocyte proliferation, IL-2 production and cell-surface IL-2 receptor (IL-2R) expression. RESULTS: Splenic lymphocyte proliferation responses to T cell mitogen, concanavalin A (Con A), were depressed from 1 to 7 days after scald injury (all P<0.05). Meanwhile, in comparison with sham scald group, burn injury resulted in a significant decrease in splenic production of IL-2 on postburn day 1, 3, as well as 5, and a marked suppression of IL-2R expression on days 1 and 3 postburn (all P<0.05). Treatment with EP after burn injury showed a dramatic restoration of lymphocyte proliferation rate and increased production of IL-2 at various time points (all P<0.05). However, treatment with EP did not affect IL-2R expression compared with scalded rats (all P>0.05). CONCLUSION: Treatment with EP could markedly elevate splenic T lymphocyte proliferation response and increase production of IL-2 following burn injury, thereby improving cell-mediated immunity in thermally injured rats with delayed resuscitation.

Animals↗
PubMed2006

Innate immune functions of microglia isolated from human glioma patients.

BACKGROUND: Innate immunity is considered the first line of host defense and microglia presumably play a critical role in mediating potent innate immune responses to traumatic and infectious challenges in the human brain. Fundamental impairments of the adaptive immune system in glioma patients have been investigated; however, it is unknown whether microglia are capable of innate immunity and subsequent adaptive anti-tumor immune responses within the immunosuppressive tumor micro-environment of human glioma patients. We therefore undertook a novel characterization of the innate immune phenotype and function of freshly isolated human glioma-infiltrating microglia (GIM). METHODS: GIM were isolated by sequential Percoll purification from patient tumors immediately after surgical resection. Flow cytometry, phagocytosis and tumor cytotoxicity assays were used to analyze the phenotype and function of these cells. RESULTS: GIM expressed significant levels of Toll-like receptors (TLRs), however they do not secrete any of the cytokines (IL-1beta, IL-6, TNF-alpha) critical in developing effective innate immune responses. Similar to innate macrophage functions, GIM can mediate phagocytosis and non-MHC restricted cytotoxicity. However, they were statistically less able to mediate tumor cytotoxicity compared to microglia isolated from normal brain. In addition, the expression of Fas ligand (FasL) was low to absent, indicating that apoptosis of the incoming lymphocyte population may not be a predominant mode of immunosuppression by microglia. CONCLUSION: We show for the first time that despite the immunosuppressive environment of human gliomas, GIM are capable of innate immune responses such as phagocytosis, cytotoxicity and TLR expression but yet are not competent in secreting key cytokines. Further understanding of these innate immune functions could play a critical role in understanding and developing effective immunotherapies to malignant human gliomas.

Journal Article↗
PubMed1993

Effect of the HELLP syndrome on maternal immune function.

The HELLP syndrome occurs in less than 1% of gravidas and is characterized by hemolysis, elevated liver enzymes and low platelet count. The status of immune function in these high-risk patients is not known but may be of great importance in better understanding the basis, if any, of immune dysfunction in pregnancy-associated hypertensive disorders and from the potential compounding effect of infection upon an already debilitated patient. We assessed maternal immune status in patients with the HELLP syndrome using conventional in vitro techniques. The results of these studies clearly show a depression of both T and B cell potential and impaired monocyte handling of intracellular pathogens (up to 33%, 11% and 17% of control values, respectively). The onset of this immunosuppression occurred before the clinical diagnosis of HELLP syndrome was made and persisted for at least 14 days after clinical resolution. Results of cell admixture studies suggest that these effects are mediated by accessory cells or their products and do not represent true lymphocyte dysfunction. The risk of opportunistic infections may therefore be increased in the patient with the HELLP syndrome because of this generalized immunosuppression and profound decrease in monocyte phagocytic and bactericidal activity.

Adult↗
PubMed2000

Immune function and incidence of infection during basic infantry training.

The effect of an 18.5-week infantry training program on health status was studied in 23 male military personnel (aged 22.0 +/- 0.5 years, mean +/- SE). Aerobic power, body composition, and immune function (including natural killer cell activity, mitogen-stimulated lymphocyte proliferation, in vivo cell-mediated immunity, and secretory immunoglobulin A levels) were measured in subjects at the beginning and end of the course. Subjects self-reported their symptoms of sickness in health logs using a precoded checklist. Data from this study indicate that subjects became leaner and maintained, but did not increase, their aerobic fitness by the end of the course. Cell function was enhanced significantly; however, in vivo cell-mediated immunity remained the same, and levels of secretory immunoglobulin A were lower by the end of the course. The incidence of infection remained stable throughout the course. These results indicate that the current pattern of infantry training does not have an adverse effect on the health status of recruits.

Adult↗
PubMed1998

[Human tumor xenografted into SCID mice and human immune function reconstitution].

OBJECTIVE: In order to observe (1) The behavior of growth and metastasis of PG and PGPTS7 in SCID mice and human immune function reconstituted mice; (2) The ability of interleukin-6 autosecreted from PGTS7 in enhancing the anti-tumor activity of the peripheral blood lymphocytes (PBL). METHODS: Xenografting of PG and PGTS7 into the subepithelial space of the SCID mice, and in some of these animals, human PBL were administrated simultaneously into the peritoneal cavities. The latent period, taken rate, growth speed, volume of the grafted tumor, incidences of metastasis in lungs and lymph nodes and serum level of human immunoglobulin of the immunity reconstituted mice were examined. RESULTS: Although tumor growth had been detected in all the experimental animals, the latent period of grafted PGTS7 was postponed and the volume of tumor mass as well as the incidence of lymph node metastasis all became lower in the immunity reconstituted mice accompanied simultaneously with a higher serum level of human immunoglobulin (HIg). CONCLUSIONS: (1) The SCID mice are good as an appropriated hosts in studying the behavior of growth and metastasis of PG and PGTS7. (2) IL-6 autosecreted from PGTS7 stimulates the proliferation and promotes the activating of PBL. It seems also able to enhance the liberation of human immunoglobulin: to suppress the growth of tumor cells and to reduced the rate of lymph node metastasis.

Animals↗