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At least 685 records · Page 38Linked to original sources
PubMed2006

Interleukin 2 regulation following semi-allogeneic bone marrow transplantation in mice.

Success of allogeneic and autologous bone marrow transplantation (BMT) is hampered by susceptibility to infection during the first two post-treatment years. Further, in treating malignant diseases, impaired anti-host reactivity for donor cells may contribute to a high rate of relapse. Both complications are a consequence of immune deficiency involving B and T lymphocytes. The present study evaluates several key parameters of the immunologic reconstitution mechanism in mice subjected to myeloablative total body irradiation following semi-allogeneic (parental) BMT. This resulted in a gradual reduction of splenic CD3, CD4 and CD8 cells until day 45 post-BMT. Concomitantly, there was an increase in monocytes and CD4+/CD8+ (double positive) cells, accompanied by a persistent elevation in the percentage of B lymphocytes. The total thymic and splenic T cell populations were reduced until day +30. The cellular reduction correlated with the poor proliferative response of the thymic and splenic cells. A decrease occurred in IL-2 mRNA expression in thymic cells during days 15-20 post-transplant, corresponding with the low level of IL-2 secretion in the spleen and thymus of the transplanted mice. In conclusion, following semi-allogeneic BMT, there was an overall immune down-regulation in the cells, gene and protein levels. Reduced immunological responsiveness following BMT reinforces the need for improving the immune dysfunction by immunotherapy post-BMT.

Animals↗
PubMed2001

Infectious morbidity in critically ill patients with cancer.

Infection frequently complicates the course of cancer treatment and often adversely affects the outcome. Patients have a greater tendency for acquiring infections caused by opportunistic microorganisms. Agents with low virulence potential may lead to invasive and often life-threatening infections because of altered host immune function. The immune dysfunction may be caused by the underlying malignancy, by antineoplastic chemotherapy, or by invasive procedures during supportive care.

Agranulocytosis↗
PubMed2002

Cytokines and depression: an analogic approach.

A growing body of evidence suggests that major depressive disorders may be accompanied by immune dysfunction and more particularly by an enhanced production of pro-inflammatory cytokines. The possible involvement of cytokines in depressive illness are based upon an analogic model. Pro-inflammatory cytokines are known to induce behavioral effects, and neuro-endocrine and immune activation similar to those observed in depression; these can be alleviated by antidepressant treatment. In this paper, we review research literature on the links between depressive illness and cytokine production and address further questions on this cytokine pathway. Further research is needed to see whether cytokines sustain specific depressive syndromes or whether cytokines induce depressive-like symptoms.

Acute-Phase Reaction↗
PubMed2000

Cytokine expression patterns distinguish HIV associated skin diseases.

AIDS is known to cause a shift of cytokines in the periphery. However, predominant cytokines in skin of patients with HIV-associated skin diseases have not been clearly defined. We hypothesized that there are distinct cytokine profiles that distinguish among the different clinical manifestations of AIDS-related skin diseases. To test this hypothesis, lesional and non-lesional skin was biopsied from 53 HIV+ patients with Kaposi's sarcoma (KS), psoriasis, and pruritus due to eosinophilic folliculitis, and from HIV negative controls with psoriasis or KS prior to therapy. Immunohistochemistry was performed with antibodies to tumor necrosis factor (TNF)-alpha, interleukin (IL)-10, interferon (IFN)-gamma, and interferon-inducible protein (IP)-10. HIV positive individuals included 10 with psoriasis, 14 with pruritus, and 15 with Kaposi's sarcoma. HIV negative controls included 12 with psoriasis and two with KS. Semi-quantitative analysis of cytokine staining was confirmed by optical density using a digital imaging system on four representative skin sections from each disease. Optical density analyses were conducted using ANOVA and t-tests. We found that epidermis overlying HIV+ Kaposi's sarcoma was hyperproliferative and was highest in IP-10, IFN-gamma, and IL-10 (P=0.0001). HIV+ pruritus was significantly highest in TNF-alpha (P=0.0001) staining. HIV+ psoriasis represented an intermediate state for all four cytokines. Normal skin adjacent to lesions showed the same relative patterns, with lower intensities. Skin diseases seen frequently in the setting of HIV and immunodeficiency have relatively distinct levels and patterns of cytokine expression that may reflect immune dysfunction, reactivity to HIV and to opportunistic infections.

Cytokines↗
PubMed2004

Reduced levels of neutralizing antibodies to Kaposi sarcoma-associated herpesvirus in persons with a history of Kaposi sarcoma.

Kaposi sarcoma-associated herpesvirus (KSHV) has been identified as the etiologic agent of Kaposi sarcoma (KS). Although KSHV is required for the development of KS, immune dysfunction is a common and important cofactor in the development of KS, as illustrated by the presence of KS in association with HIV infection or immunosuppressive-drug treatment after transplantation. Because neutralizing antibodies (NAb) constitute an important component of an antiviral immune response, we examined the functionality of the humoral immune response associated with KS, by measuring KSHV NAb titers in 3 groups of subjects. Group 1 included subjects who were KSHV positive, KS positive, and human immunodeficiency virus (HIV) positive; group 2 included subjects who were KSHV positive, KS negative, and HIV positive; and group 3 included subjects who were KSHV positive, KS negative, and HIV negative. NAb titers were significantly lower among subjects with KS, compared with subjects who were infected with KSHV but who did not have clinical evidence of KS, in a multivariate model adjusted for HIV infection and CD4 T cell count. The data from the present study suggest that NAb may play a role in the control of KSHV infection and the prevention of progression of KSHV infection to KS.

Adult↗
PubMed2004

Autoimmunity, anergy, lentiviral immunity and disease.

Autoimmune antibodies and autoimmune responses have been characterized in both human HIV infection and the rhesus macaque (RM) non-human primate model of SIV infection and reasoned to contribute to the pathogenesis of AIDS. Many theories for the induction and maintenance of such responses have been entertained including molecular mimicry between HIV proteins and self molecules, CD4+ T cell loss accompanied by loss of normal immune regulation that dictate self-non-self-reactivity, defective negative/positive selection of T cells to name a few. The precise mechanisms that lead to such immune dysfunction is difficult to study in humans. Our lab has been studying such autoimmune responses in both SIV-infected RM and sooty mangabeys (SM), a species from Africa that are naturally infected with SIV but do not display any detectable signs of immune deficiency or autoimmunity. We submit that this model is an important model since it allows for narrowing down those mechanisms and pathways that are a result of lentiviral infection per se from those that specifically cause disease including autoimmunity. During the course of these studies, we have ruled out a role for plasma and cellular viral loads, anti-viral humoral responses and a variety of cell signaling pathways. We have identified select pathways that appear to play roles in the pathogenesis of lentiviral infection and disease. These include pathways involved in innocent bystander killing by apoptosis of CD4+ T cells, role for differential regulation of the cell cycle, and a role for distinct host proteins that get incorporated by the virions as they are assembled and either bud out of CD4+ T cells or exit the cells in the form of multi-vesicular endosomal particles from monocytes/macrophages from SIV-infected disease susceptible RM and disease-resistant SM. We present our current working model and hypotheses that are designed to elucidate differences that are responsible for such distinct outcomes of lentiviral infection, autoimmunity and disease. We believe that such findings have important implications for the design of vaccines against human HIV infection.

Autoimmunity↗
PubMedDate not supplied

Foods, diet, and skin diseases.

Human skin is continuously exposed to internal and external influences that may alter its condition and functioning. As a consequence, the skin may undergo alterations leading to immune dysfunction, imbalanced epidermal homeostasis, or other skin disorders. New theories are developing that link food intake and health. The objective of this review is to evaluate current knowledge about the interrelation of food and skin, particularly the effect of nutrients on some cutaneous immune disorders and therapeutic actions of nutrients in skin disorders.

Autoimmune Diseases↗
PubMed2001

AIDS-related malignancies.

Immunodeficiency alters the risk of cancer. Specific types of immune dysfunction are associated with different tumor risks, but most tumors are related to oncogenic viruses. In acquired immunodeficiency due to the human immunodeficiency virus (HIV), HIV itself rarely directly causes cancer; rather, it provides the immunologic background against which other viruses can escape immune control and induce tumors. The most common malignancies are Kaposi's sarcoma and non-Hodgkin's lymphoma. This chapter discusses the pathophysiologic background of these tumors, how they have been affected by the use of anti-HIV medications, and their clinical management.

Acquired Immunodeficiency Syndrome↗
PubMed2002

Nutrition beyond nutrition: plausibility of immunotrophic nutrition for space travel.

BACKGROUND AND AIMS: Microgravity has adverse effects on the immune system. We examined the effects of supplemental dietary nucleotides on immune function in ground-based in vivo anti-orthostatic tail-suspended (AOS) mice and in vitro (bioreactor-BIO) analogs of microgravity. METHODS: BALB/c mice were divided into the following three groups: group housed, single isolation, and AOS. Mice were fed either control chow or chow supplemented with RNA or uracil. Immune function was assessed by in vivo popliteal lymph node proliferation (PLN), in vitro PHA-stimulated proliferation of splenocytes and cytokine production. BIO splenocytes were cultured in vitro with/without PHA, a nucleoside-nucleotide mixture (NS/NT) or uridine. The cell proliferation and scanning electron microscopic examination for cells were carried out. RESULTS: PLN response was significantly suppressed in AOS mice (P<0.05) and was restored by RNA and uracil diets. Splenocytes from AOS mice had decreased phytohemagglutinin (PHA)-stimulated proliferation, decreased IL-2 and IFN-gamma cytokine levels (P<0.05). These responses were restored by RNA and uracil diets. In BIO cultures, PHA response was suppressed significantly, and uridine and NS/NT restored the proliferative responses. Scanning electron microscopic analysis of cells cultured in BIO revealed cells with pinched, distorted and eroded membranes. Nucleotide supplementation especially uridine restored normal activated cell surface appearance and ruffling. CONCLUSION: In the microgravity analog environment of AOS and BIO, supplemental nucleotides and especially uracil/uridine have up-regulating and immunoprotective effects with potential as a countermeasure to the observed immune dysfunction in true microgravity.

Animals↗
PubMed2005

Diminished expression and function of TLR in lymphatic filariasis: a novel mechanism of immune dysregulation.

Lymphatic filariasis is a disease characterized by immune dysregulation involving APC and T cell populations. To assess the contribution of TLR in mediating this dysregulation, we examined the expression of TLR1, TLR2, TLR4, and TLR9 on B cells and monocytes of filaria-infected and uninfected individuals. Baseline expression of TLR was significantly lower in B cells but not in monocytes of the filaria-infected group compared with the uninfected group. Upon stimulation with filarial Ag, a diminished up-regulation of TLR was observed in both B cells and monocytes of infected individuals. Finally, stimulation of B cells and monocytes with TLR ligands resulted in decreased B cell and monocyte activation/cytokine production, indicating a state of immune tolerance. This dysregulation is associated with diminished CD4(+) T cell production of IFN-gamma and IL-5. The diminished expression and function of TLR is thus a likely consequence of chronic Ag stimulation and could serve as a novel mechanism underlying the dysfunctional immune response in filariasis.

Adult↗
PubMed2001

Retroviral vectors for gene therapy of AIDS and cancer.

Both AIDS and cancer are linked to immune dysfunctions of the body which are characterized by the persistence of disease-afflicted cells. To effect a cure with novel gene therapy approaches, these diseased cells must be eliminated either directly or indirectly using cytotoxic or suicide genes, or via activation of specific immune functional cells. Retroviral vectors are useful tools for long-term genome modification owing to their ability to integrate into host chromosomes. However, most oncoretroviruses, including murine leukemia virus (MLV), require cell division to facilitate nuclear entry; this has restricted the application of murine oncoretroviral vectors to cell targets that are actively dividing. Accordingly, gene transfer into hematopoietic stem cells (HSCs) and terminally differentiated cells such as muscles, neurons and dendritic cells (DCs) has been limited with the conventional oncoretroviral vectors. The lentiviral family of retroviruses, including human immunodeficiency virus type 1 (HIV-1), has been developed into useful gene transfer tools. Lentiviral vectors carry several nuclear entry viral proteins, and therefore can target slowly-dividing and non-dividing cells. To activate immune response against cancer or HIV infection, long-term marking of the target cells is not necessary. However, to establish intracellular defense to prevent HIV infection, prolonged genetic modification of target cells such as HSCs will be required. Due to the poor transduction efficiency and the problem of transgene silencing over time with oncoretroviral vectors, most gene therapy studies for AIDS and cancer using oncoretroviral vectors remain proof-of-concept studies. Here we will discuss recent developments in the use of retroviral vectors, including HIV-1-derived lentiviral vectors, for the treatment of AIDS and cancer, and their future therapeutic potential.

Acquired Immunodeficiency Syndrome↗
PubMedDate not supplied

Mice transgenic for simian immunodeficiency virus nef are immunologically compromised.

An intact nef gene is essential for rapid development of immunodeficiency in human immunodeficiency virus and simian immunodeficiency virus infections. To assess the role of nef in the immune response, mice transgenic for SIV nef were constructed and the humoral and cellular immune response to herpes simplex virus type-1 (HSV-1), measured. Mice transgenic for SIVmac239 nef exhibited a significantly increased mortality rate when challenged with HSV-1 and also showed unusual antibody kinetics in response to viral challenge. During a 32-week period following exposure to HSV, it was noted that IgG subclass titers continued to rise in the nef+ animals, while titers of nef- animals decreased. Additionally, following secondary challenge with HSV, nef- mice had a significantly greater rise in HSV-neutralizing antibody titers than nef+ mice. A decreased proliferative response to the T cell mitogen, PHA, was noted in the nef+ animals. These results suggest that the presence of nef+ is sufficient to induce immune dysfunction.

3T3 Cells↗
PubMed1996

Immunomodulation by pycnogenol in retrovirus-infected or ethanol-fed mice.

Pycnogenol is a commercial mixture of bioflavonoids that exhibits antioxidative activity. The effects of dietary pycnogenol on immune dysfunction in normal mice as well as those fed ethanol or infected with the LP-BM5 murine retrovirus were determined. The ethanol consumption and retrovirus infection caused abnormalities in the function and/or structure of a broad array of cells involved in humoral and cellular immunity. Pycnogenol enhanced in vitro IL-2 production by mitogen-stimulated splenocytes if its production was suppressed in ethanol-fed or retrovirus-infected mice. Mitogenesis of splenocytes did not show a significant change in mice treated with pycnogenol. It reduced the elevated levels of interleukin-6 produced in vitro by cells from retrovirus infected mice and IL-10 secreted by spleen cells from mice consuming ethanol. Natural killer cell cytotoxicity was increased with pycnogenol treatment.

Adjuvants, Immunologic↗
PubMed1992

The effect of erythropoietin in normal healthy volunteers and pediatric patients with burn injuries.

BACKGROUND: Surgical procedures result in blood loss that can require replacement transfusions. Such therapy may result in multiple adverse sequelae, including transmission of infectious diseases and immune impairment. Alternative therapies are therefore desirable. METHODS: We evaluated the ability of recombinant human erythropoietin (rEPO) to increase red blood cell production in both normal healthy volunteers and patients with burn injuries. The effect of rEPO on immune function in the volunteers was also evaluated. The volunteers received 150 units/kg rEPO daily for 7 days, with immune function and hematopoiesis assayed on days 0, 7, and 14. The patients with burn injuries received either 500 units/kg/day rEPO with iron supplementation or merely the iron. RESULTS: rEPO increased erythropoiesis in both the volunteers and the patients with burn injuries. Failure to provide iron supplementation to the volunteers resulted in significant depletion of iron stores with a concomitant impairment in immune function that paralleled the iron depletion. CONCLUSIONS: rEPO therapy offers the potential to increase red blood cell production in surgical patients. Failure to provide iron supplementation in patients receiving rEPO can lead to a rapid depletion of iron stores and may contribute to an immune dysfunction.

Adult↗
PubMed1995

[Clinical aspects of immunoneuroendocrine alterations in HIV infection].

A number of studies confirm that any human tissue can be targeted by HIV, and also the endocrine system is involved during HIV infection. No endocrine adenus is saved by the assault of the opportunistic pathogens that overrun the organism unprotected due to the severe and progressive immune deficits induced by the HIV. As a consequence clinical, but often subclinical alterations can be detected that underline the close relationship among the systems of body adaptation to the environment (immune, endocrine, and nervous). Indeed these alterations can be viewed as an immunoneuroendocrine pathology. AIDS is a paradigmatic syndrome for the variety of immune dysfunctions, and also presents endocrine and neurological dysfunctions, which allow to better understand the connections among these systems, and the interactions of HIV with the immunoneuroendocrine dynamics.

Endocrine Glands↗
PubMed2006

A new wrinkle: skin manifestations of aging may relate to autonomic dysfunction.

Various mechanisms have been argued for skin wrinkling, one of the hallmarks of aging. We hypothesize that chronic sympathetic bias is a previously unrecognized mechanism for wrinkling. In the acute setting of water immersion, reversible skin wrinkling is a well-known reflex mediated by the autonomic nervous system. We postulate that skin wrinkling results as a local maladaptive manifestation of a global chronic sympathetic bias that emerges during aging. The persistence of such changes may induce additional compensatory remodeling to cause permanent alteration of the skin. Sympatholytic agents may prove beneficial for arresting or ameliorating the development of wrinkles. Conditions that amplify sympathetic bias such as stress, smoking, amphetamine abuse, HIV, heart failure, and transplantation may accelerate wrinkling. Other common diseases of the skin may also arise as particular manifestations of aberrant autonomic activity through induction of vascular and immune dysfunctions. The temporal and spatial distribution of these dermatologic conditions may reflect variation of autonomic balance, which also regulates T helper immune balance. For all of these dermatologic conditions, local and systemic administration of drugs and medical devices that pharmacologically or electrically modulate autonomic nervous system activity may yield benefits as well.

Aging↗
PubMed2003

Sex differences in infection and sepsis.

Sex and gender-based differences in responses to infection and sepsis are evident. Estrogens increase immune function, sometimes to the point of inducing autoimmune disease. Testosterone suppresses immune function, sometimes leading to a worsened outcome following traumatic injury. Therapies using sex hormones to improve outcomes after sepsis and hemorrhagic shock and to reduce exacerbations of autoimmune diseases are being studied. Differences in sex hormone levels may not tell the whole story. Studies of immune function in girls and boys before puberty may be helpful. Differences found early might indicate that factors other than estrogen and androgen levels are contributing. Variations in societal role acculturation and exposures that are gender based also may be involved. Clinicians must consider sex and gender when attempting to determine the risk of infection, sepsis, and immune dysfunction in populations. Clinical applications of sex and gender differences are just beginning to occur with the genesis of sex hormone-based treatments. The large-scale efficacy of such treatments has yet to be reported. Innovative strategies based on sex or gender differences in immune responses may soon be available and may lead to essential data for clinical decision making. The impact of sex and gender differences on long-term health outcomes remains to be seen.

Female↗
PubMed1985

The Vancouver Lymphadenopathy-AIDS Study: 3. Relation of HTLV-III seropositivity, immune status and lymphadenopathy.

In a study of 394 homosexual men recruited at the primary care level the prevalence of antibody to human T-lymphotropic retrovirus (HTLV-III) was higher among those with lymph node enlargement than among controls. The degree of abnormal immune function, as shown by abnormalities in immunoglobulin levels, immune complex activity and T-lymphocyte subsets, was correlated with the extent of lymphadenopathy. A similar pattern of immunologic abnormality was associated with seropositivity for HTLV-III antibody. However, HTLV-III seropositivity was the major determinant of immune function after adjustment for lymph node status. The results suggest that the immune dysfunction seen in patients with lymphadenopathy is due for the most part to the high prevalence of HTLV-III seropositivity in these populations. Lymphadenopathy, in many subjects, may in fact represent a physical sign of a stabilized compensated homeostatic host response. Factors responsible for severe immune decompensation associated with acquired immune deficiency syndrome (AIDS) may best be sought by prospective study of HTLV-III seropositive asymptomatic patients or those with stable persistent generalized lymphadenopathy and relatively normal immune function.

Acquired Immunodeficiency Syndrome↗