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PubMed1987

Analysis of heavy metal immunotoxicity by multiparameter flow cytometry: correlation of flow cytometry and immune function data in B6CF1 mice.

Bone marrow and spleen cells obtained from female B6C3F1 mice given a single i.p. exposure to cadmium acetate (0.9 mg/kg), lead acetate (12 mg/kg), or sodium acetate (12 mg/kg), were studied using flow cytometry, immunologic, and hematologic assays. Significant changes were detected in subpopulations of bone marrow cells using multiparameter flow cytometry within 1 day following treatment with cadmium or lead. Bone marrow cells obtained from B6C3F1 mice 5 days after treatment with cadmium or lead were found to have a decreased number of cells expressing Mac-1, 55-7.2, 14.8, and Lyt-1 antigens, suggesting a shift to immature cell types. An increase in the number of progenitor cells (CFU-C) obtained from the bone marrow of mice treated with heavy metals was also noted 5 days after exposure to cadmium or lead. A time-dependent suppression of the in vitro primary humoral immune response of spleen cells to SRBCs, TNP-Ficoll and TNP-LPS was produced by cadmium or lead treatment. Suppression of the mitogenic response of spleen cells to Con A, PHA, and LPS was also found to be time-dependent. Spleen cell surface marker expression (Mac-1, Lyt-1, Lyt-2 and 14.8) was altered in response to cadmium or lead treatments, but these changes did not appear to correlate with the humoral immunity or mitogen-induced proliferation data. These studies demonstrate that changes in cell surface markers on discrete subpopulations of lymphoid cells present in the spleens of heavy metal exposed mice may not correlate with alterations in the functional activity of these cells. However, changes in murine bone marrow surface markers in response to cadmium or lead treatment predicts a shift to immature cell types, which appeared to correlate with the increase in CFU-C activity.

Acetates↗
PubMed2006

Opposite immune functions of GM-CSF administered as vaccine adjuvant in cancer patients.

Granulocyte-macrophage colony-stimulating factor (GM-CSF) has been and is still widely used as an adjuvant in clinical trials of vaccination with autologous tumor cells, peptides and/or dendritic cells in a variety of human neoplasms. This cytokine was administered either as product of gene-transduced tumor cells or as recombinant protein together with the vaccine given subcutaneously or intradermally. Results of these trials were heterogeneous in terms of induction of vaccine-specific immune response and of clinical response. Though in some of these studies GM-CSF appeared to help in generating an immune response, in others no effect or even a suppressive effect was reported. Here, we review the literature dealing with the immune adjuvant activity of GM-CSF both in animal models and clinical trials. As a consequence of such analysis, we conclude that GM-CSF may increase the vaccine-induced immune response when administered repeatedly at relatively low doses (range 40-80 microg for 1-5 days) whereas an opposite effect was often reported at dosages of 100-500 microg. The potential mechanisms of the GM-CSF-mediated immune suppression are discussed at the light of studies describing the activation and expansion of myeloid suppressor cells by endogenous tumor-derived or exogenous GM-CSF.

Adjuvants, Immunologic↗
PubMed1994

Immunomodulating activities of cocaine--evaluation of lymphocyte transformation related to other immune functions.

Cocaine dosages ranging from 2.5 mg/kg/day to a highly toxic dose of 50 mg/kg/day were injected intramuscularly or intraperitoneally into different groups of mice for 4-10 days. The effects of cocaine were evaluated by tumor growth, lymphocyte transformation, phagocytosis, and IgM plaque-forming cells. At all dosages, including toxic doses, cocaine does not inhibit lymphocyte transformation of the splenic or the peripheral blood lymphocytes. However, all other immunological parameters of the same animal were suppressed. These results suggest that lymphocyte transformation may not be a proper indicator for the immune status of mice treated with cocaine. The same may be true when testing human drug abusers.

Adjuvants, Immunologic↗
PubMed1992

Cognition and immune function in HIV-1 infection.

OBJECTIVES: To determine (1) whether there were differences in cognition between HIV-1-seropositive and HIV-1-seronegative homosexual men and (2), if so, whether these differences could be explained by the degree of immunosuppression [i.e., CD4 cell count and immunoglobulin A (IgA) levels]. DESIGN: A cross-sectional design was used to compare 66 HIV-1-seropositives (Centers for Disease Control stages II and III, n = 56; stages IVA and IVC-2, n = 10) and 37 HIV-1-seronegatives. The HIV-1-seropositives were classified into three immune groups based on their CD4 cell count (x 10(6)/l) and serum IgA level (mg/dl): (1) moderate [(n = 35) CD4 greater than 400, IgA less than 300]; (2) mixed [(n = 22) either CD4 greater than 400 and IgA greater than 300 or CD4 less than 400 and IgA less than 300] and (3) poor [(n = 9) CD4 less than 400, IgA greater than 300]. HIV-1-seronegatives formed the 'good' immune group (CD4 greater than 400 and IgA less than 300). METHODS: The four groups were compared on tests of verbal and visual memory, information-processing speeds, visuospatial skills, language processes, attention, psychomotor reaction time, and mental status. Factors other than HIV-1 sero-status that can influence cognitive performance were tested as covariates. RESULTS: HIV-1-seropositives had slower information-processing speeds and decreased verbal and visual memory, compared with HIV-1-seronegatives. These differences in cognition were not due to differential immunosuppression or to clinical status among the HIV-1-seropositives. CONCLUSIONS: Cognitive alterations occur in HIV-1-infected individuals before AIDS and appear to be independent of clinical status and degree of immunosuppression as measured by CD4 cell count and IgA levels.

Adult↗
PubMed1981

Antigranulocyte antibodies and deranged immune function associated with phenytoin-induced serum sickness.

A phenytoin-associated serum-sickness-like syndrome was followed by severe pancytopenia in a 17-year-old female. Serum obtained during the acute phase of her illness contained antibodies against homologous eosinophils and neutrophils, antibodies against autologous neutrophils, and antibodies to phenytoin. The serum also inhibited bone marrow granulocyte colon formation in vitro. Lymphocyte transformation by pokeweed mitogen was impaired and, after recovery, the patient's lymphocytes were transformed in vitro by the addition of phenytoin. These data demonstrate that profound derangements of immunity can be associated with a phenytoin-induced serum-sickness-like illness.

Adolescent↗
PubMedDate not supplied

Interleukin-7 (IL-7): immune function, involvement in the pathogenesis of HIV infection and therapeutic potential.

Interleukin 7 (IL-7), which is constitutively produced particularly by stromal cells from the bone marrow and thymus, plays a crucial role in T cell homeostasis. This cytokine is implicated in thymopoiesis since it sustains thymocyte proliferation and survival. It regulates peripheral naive T cell survival by modulating the expression of the anti-apoptotic molecule Bcl-2, and sustains peripheral T cell expansion in response to antigenic stimulation. Infection by the human immunodeficiency virus (HIV) leads to severe T lymphopenia and general immune dysfunction. Increased IL-7 plasma levels are generally observed in HIV-infected patients. The existence of an inverse correlation between IL-7 plasma levels and the CD4+ T cell count suggests that a direct feedback mechanism is working to restore peripheral T cell counts in lymphopenic patients. Here, IL-7 plasma levels are a good predictive marker of CD4+ T cell restoration during therapy. Combinations of antiretroviral treatments considerably slow disease progression. They drastically decrease the viral load and, in most patients, significantly increase peripheral CD4+ T cell counts. However, despite their usual ability to reduce viral replication, such treatments often fail to reverse lymphopenia and do not restore specific antiviral immune responses. IL-7, based therapy, combined with efficient antiretroviral treatment, may be beneficial to HIV-infected patients by promoting thymic output, sustaining naive T cell counts and increasing memory T cell activation.

Antiretroviral Therapy, Highly Active↗
PubMed1988

Relationship between acupuncture-induced immunity and the regulation of central neurotransmitters in the rabbit: I. Effect of central catecholaminergic neurons in regulating acupuncture-induced immune function.

The central catecholaminergic neurons play an important role in the promotion of the T-lymphocyte transformation and the regulation of the positive rate of acid a-naphthylacetate esterase (ANAE) activity with acupuncture. The mechanism by which acupuncture promotes the T-lymphocyte transformation function may be principally by promoting the anabolism of the T-lymphocyte and speeding up the anabolism of the DNA. Judging from the fact that acupuncture increases the positive rate of ANAE, it can be assumed that the quantity of T-lymphocyte was increased markedly. It remains to be clarified what links exist through which the central catecholaminergic neurons can influence the acupuncture induced immunity, and what the effect of other transmitter neurons of the central nervous system are on acupuncture induced immunity.

Acupuncture Therapy↗
PubMed1983

Clinical outcome as assessed by anthropometric parameters, albumin, and cellular immune function in high-risk infants receiving parenteral nutrition.

Twelve infants with underlying gastrointestinal tract disorders receiving 16 courses of total parenteral nutrition were retrospectively studied. Stratification according to calorie intake provided the best means for discriminating among different outcomes. Infants receiving greater than 110 calories/kg/d experienced significantly greater increases in weight, mid-arm muscle circumference, and triceps and subscapular skinfold thicknesses than did infants receiving less than 110 calories/kg/d. Catch-up growth was only seen in infants with intakes of greater than 110 calories/kg/d. In nine of these 12 infants, in vitro cellular immune parameters were assayed. Infants in both the high- and low-calorie groups experienced similar increases in transformational responses to pokeweed mitogen (PWM) and phytohemagglutinin (PHA) and in the percentage of peripheral blood T lymphocytes. No increase in serum albumin was seen regardless of calorie intake.

Anthropometry↗
PubMed1986

The graft-versus-host reaction and immune function. IV. B cell functional defect associated with a depletion of splenic colony-forming units in marrow of graft-versus-host-reactive mice.

Studies were conducted to determine whether a functional B cell defect occurred in the bone marrow of mice experiencing a GVH reaction (GVHBM). GVH reactions were induced in AxCBA F1 adult mice by an injection of A strain lymphoid cells. The GVH reaction was confirmed by immunosuppression and thymus histology. At various intervals after GVH induction, GVHBM was tested for its ability to restore B cell function in adult thymectomized irradiated mice reconstituted with normal thymocytes. GVHBM cells obtained seven days after GVH induction restored but slightly the plaque forming cell (PFC) response to sheep erythrocytes and the mitogen response to lipopolysaccharide (LPS). GVHBM cells obtained 10 days or later failed to reconstitute the PFC or LPS responses. GVHBM cells suppressed neither the T or B cell function of normal spleen cells nor the LPS mitogen response of normal bone marrow cells. In addition, the splenic colony-forming units (CFU-s) in GVHBM were slightly decreased by day 10 after GVH induction and markedly depressed by day 22 after GVH induction. These results suggest that the GVH reaction may affect two different events in B cell differentiation. The early decrease in functional B cells that occurs before there is any change in the CFU-s population suggests a direct effect on B cell production, whereas the later absence of functional B cells could be due to the marked decline in stem cell production (CFU-s).

Animals↗
PubMed2003

Interaction of bifidobacteria with the gut and their influence in the immune function.

Bifidobacteria are predominant in the lumen of the large intestine and confer various health benefits on the host. They are also used in the preparation of new fermented milks (bioyogurts) or added to conventional yogurt to generate probiotic effects. The colonization of the gut by bacteria tends to be host specific due partly to the way in which bacteria adhere to the intestinal wall. Using a homologous strain of Bifidobacterium animalis in an experimental mouse model, we analyzed by immunofluorescence labelled-bacteria and transmission electronic microscopy the importance of the bacterial interaction with epithelial an immune cells associated to the gut, and the effect of feeding of B. animalis in the immune response. It was able to adhere and interact with both small and large intestine. In spite of this interaction with the gut, no modifications in the immune state (secretory or systemic response) were observed. A heterologous strain of Bifidobacterium adolescentis from human faeces, was neither incapable of binding to the intestine, nor influence the immune system activation, when it was administered during 2, 5 or 7 consecutive days; we believe that using a homologous strain, oral tolerance is developed even when the microorganism interacts with the immune cells associated with the intestine. However, we cannot ignore the beneficial effect of these microorganisms, especially in the prevention of intestinal infections. We think that this property exerted by bifidobacteria is more related to other mechanisms such as competitive inhibition, acid production or others, than enhancement of the immune state.

Animals↗
PubMed1996

Stress, immune function, and relationship to pregnancy outcome.

Pregnancy and the postpartal period are a time of immunosuppression. The normal immunosuppression that occurs during the puerperium may be aggravated by stress. Normal mechanisms of immunosuppression are discussed, and the research related to stress and childbearing is examined in this article.

Antibody Formation↗
PubMed2006

Ribonucleotides: conditionally essential nutrients shown to enhance immune function and reduce diarrheal disease in infants.

It remains a goal of pediatric nutrition to provide optimal nourishment for infants who are not fed human milk. Investigators have attempted to emulate the composition and functionality of human milk, the gold standard for infant nutrition. These efforts began with the analysis of milk components and continued with assessments of biological effects that culminated in clinical studies in infants. This chapter summarizes the path that researchers followed to study ribonucleotides and their role in infant nutrition. Based on analytical methods for the quantification of ribonucleotides in human milk, investigators assessed their potential impact on the immune systems of infants and looked for concomitant mechanistic explanations. These inquiries evolved into clinical trials in which ribonucleotide-supplemented formula performance was compared with that of non-supplemented formulas and with human milk. This chapter intends to summarize an area of pediatric nutrition that has yielded both enlightening evidence and seemingly contradictory data.

Diarrhea, Infantile↗
PubMedDate not supplied

[Role of Mg2+ in keeping up the nonspecific immune functions of human neutrophils in vitro during hyperbaric exposure].

Earlier we have shown inhibition of the production by neutrophils of active forms of oxygen in humans exposed to high pressure. To get better understanding of the role of Mg2+ in the process, magnitude of the effect was assessed as a function of Mg2+ concentration using the activated hemiluminescent technique. It appears that in vitro production of active oxygen forms by blood neutrophils at high pressures can be sustained provided increased concentrations of Mg2+ in the incubating medium.

Atmospheric Pressure↗
PubMed2005

Immune function responds to selection for cuticular colour in Tenebrio molitor.

Cuticular colour in the mealworm beetle (Tenebrio molitor) is a quantitative trait, varying from tan to black. Population level variation in cuticular colour has been linked to pathogen resistance in this species and in several other insects: darker individuals are more resistant to pathogens. Given that cuticular colour has a heritable component, we have taken an experimental evolution approach: we selected 10 lines for black and 10 lines for tan adult cuticular phenotypes over at least six generations and measured the correlated responses to selection in a range of immune effector systems. Our results show that two immune parameters related to resistance (haemocyte density and pre-immune challenge activity of phenoloxidase (PO)) were significantly higher in selection lines of black beetles compared to tan lines. This may help to explain increased resistance to pathogens in darker individuals. Cuticular colour is dependent upon melanin production, which requires the enzyme PO that is present in its inactive form inside haemocytes. Thus, the observed correlated response to selection upon cuticular colour and immune variables probably results from these traits' shared dependence on melanin production.

Analysis of Variance↗
PubMed2000

Comparison of inhibitory effects of local anesthetics on immune functions of neutrophils.

Immunological effects of a variety of local anesthetics on adhesion, phagocytosis, and the production of superoxide anion and hydrogen peroxide by neutrophils were compared. Neutrophils were isolated by peritoneal lavage from rats, 4 h after injection of 1% glycogen. Lidocaine, mepivacaine, procaine, prilocaine and tetracaine at 1 mg/ml inhibited adhesion, phagocytosis, and the production of superoxide anion and hydrogen peroxide in neutrophils. Moreover, lidocaine, mepivacaine, procaine and prilocaine at 0.1 mg/ml inhibited the production of superoxide anion and hydrogen peroxide but not adhesion or phagocytosis. In contrast, tetracaine at 0.1 mg/ml inhibited phagocytosis, and the production of superoxide anion and hydrogen peroxide but not adhesion. At 0.01 mg/ml, however, tetracaine inhibited the production of superoxide anion and hydrogen peroxide; in contrast, other drugs failed to affect neutrophil function. These results suggest that the local anesthetics may affect adhesion, phagocytosis, and the production of superoxide anion and hydrogen peroxide by neutrophils.

Anesthetics, Local↗
PubMed2004

A novel assay to detect nucleotide receptor P2X7 genetic polymorphisms influencing numerous innate immune functions.

The importance of accessory signaling pathways amplifying endotoxin responses has recently been highlighted by genetic studies describing LPS-hyporesponsive individuals despite carrying the common allele for TLR4. The nucleotide receptor P2X7 modulates the production of numerous LPS-stimulated inflammatory mediators. We have recently described the largest phenotypic screen known for genetic polymorphisms associated with the nucleotide receptor P2X7, a global regulator of leukocyte function. This required the development of a novel monocyte pore assay with numerous advantages over previous methods and with the potential to facilitate rapid (< 3 h), multiplex analysis of clinical samples. This paper addresses aspects pertinent to the development of the monocyte pore assay, briefly summarizes our results suggesting that P2X7 alleles modulate LPS-stimulated cytokine production, and discusses a model wherein P2X7 may serve as an amplification loop of innate immunity.

Amino Acid Substitution↗