Immune parameters in biological monitoring of pesticide exposure: current knowledge and perspectives.

Exposure to pesticides can cause a number of effects on the immune system, varying from a slight modulation of immune functions to the development of clinical immune diseases. The aim of this study has been reviewing published data on immune effects of pesticides in humans, with particular attention for effects observed in absence of any other change, and to the possibility of identifying a dose effect relationship. Some evidence of immunotoxic effects in man involve organophosphorus compounds, some organochlorine insecticides (OC), some carbamates, some phenoxy herbicides, dithiocarbamates, and pentachlorophenol (PCP).

Tumour necrosis factor (TNF) and TNF-related molecules in HIV-1+ individuals: relationship with in vitro Th1/Th2-type response.

We examined the secretion and expression by peripheral blood mononuclear cells (PBMC) of TNF-alpha and TNF-related molecules with regard to Th1/Th2-type cytokine production. In 76 HIV+ patients at different disease stages and in 25 controls we measured cytokine (TNF-alpha/beta, interferon-gamma (IFN-gamma), IL-2, IL-4, IL-10), and activation marker secretion (sCD4, sCD8, sCD30) in phytohaemagglutinin (PHA)-stimulated and unstimulated PBMC cultures by ELISA, and membrane-bound TNF-alpha and CD30 expression by flow cytometry. We found an expansion of the TNF system in HIV+ individuals, that positively correlated with TNF-alpha, IFN-gamma and sCD8, probably representing activation of the cytotoxic compartment.

[Immunotoxicology in occupational and environmental medicine: prospectives, limitations, and research objectives].

The immune system is able to recognize and neutralize potentially harmful agents, conferring to the organism resistance to infectious and malignant diseases. The authors have reviewed the literature and identified a group of substances able to enhance and/or reduce different immune functions, both in an experimental model and in occupational and environmental human exposure. The group includes several polyhalogenated hydrocarbons, particularly polychlorinated biphenyls, polybrominated biphenyls, tetrachloro-dibenzo-p-dioxin (TCDD), some metals like lead, cadmium and mercury, pesticides, i.

Soluble CD30, tumour necrosis factor (TNF)-alpha, and TNF receptors in primary HIV-1 infection: relationship with HIV-1, RNA, clinical outcome and early antiviral therapy.

The natural course of human immunodeficiency type 1 (HIV-1) infection varies considerably. The identification of laboratory disease markers has become critically important to patient management. This study, carried out on 37 patients with primary HIV-1 infection (PHI), shows that, along with plasma HIV-1 RNA and CD4+ T cell counts, evaluation of plasma levels of some immune activation markers (sCD30, TNF-alpha, and sTNFR-I) may help to identify patients at risk of a more rapid disease progression, suggesting that immune activation is among the factors who determine the rate of disease progression.

Immunomodulatory effects of occupational exposure to mancozeb.

The effects of occupational exposure to ethylene-bis-dithiocarbamate of manganese and zinc on the immune system were evaluated in a group of mancozeb-exposed manufacturers and controls. The immune system tests revealed the following: (a) lymphocyte proliferative responses triggered by different activators and mitogen-induced IL-2 production were higher in exposed subjects than in controls; (b) production of monocyte/macrophage-derived IL-1 and polyclonal IgG and IgM, by beta-lymphocytes, did not differ between exposed subjects and controls; (c) percentages and absolute numbers of total T-cells, T-helper cells, T-suppressor/cytotoxic cells, activated T-cells, total beta-cells, and natural killer cells were similar in exposed subjects and controls; (d) serum immunoglobulin classes and complement fractions were within the range of normality; and (e) rheumatoid factor and non-organ-specific serum autoantibodies were absent in exposed and control subjects. An increase in T-cell functional response was found in the exposed group, suggesting a slight immunomodulator effect of mancozeb in conditions of low-level, prolonged occupational exposure.

Plasma levels of soluble CD30, tumour necrosis factor (TNF)-alpha and TNF receptors during primary HIV-1 infection: correlation with HIV-1 RNA and the clinical outcome.

Objectives: The immunological and virological events associated with primary HIV-1 infection have a major impact on the course of HIV-1 disease, and the identification of early predictors during primary HIV infection is critical for the therapeutic strategy.

Design And Methods: Eighteen consecutive patients with primary HIV infection were followed for a median of 398 days. Clinical status, CD4+ T-cell counts, and plasma samples were obtained weekly from enrollment until week 6, then at weeks 12, 24 and 52, and every 6 months thereafter.

Immunosuppressive activity of 15-deoxyspergualin on normal and autoimmune peripheral blood mononuclear cells.

Several experimental conditions were used in this study to evaluate the in vitro effects of 15-deoxyspergualin on the function of T lymphocytes, B lymphocytes and monocytes from healthy subjects and patients suffering from systemic lupus erythematosus. Whilst the secretion of polyclonal immunoglobulin (Ig) M and IgG from the B lymphocytes of the healthy subjects was diminished by 15-deoxyspergualin, neither the proliferative response of normal T and B cells to mitogenic stimulation nor the cytokine secretory capacity of these cells (e.g.

Synergistic effect of deoxyspergualin (DSP) and cyclosporin A (CsA) in the prevention of spontaneous autoimmune diabetes in BB rats.

Dose-dependent side effects are frequently observed with immunosuppressive drugs of potential relevance for the immunotherapy of insulin-dependent diabetes mellitus (IDDM), such as CsA and DSP. If CsA and DSP acted synergistically in vivo, their combined use would allow using each compound at lower doses than those required when each drug is given in monotherapy. Consequently, dose-dependent side effects could be reduced and the therapeutic activity maintained or even enforced.

Interleukin-10-induced HIV-1 expression is mediated by induction of both membrane-bound tumour necrosis factor (TNF)-alpha and TNF receptor type 1 in a promonocytic cell line.

Objective: To investigate whether the upregulatory effect of interleukin (IL)-10 on HIV expression in a model of latent HIV infection is mediated by induction of endogenous tumour necrosis factor (TNF)-alpha and TNF receptors (TNFR).

Design: The latently HIV-infected promonocytic cell line U1 was examined, because in this in vitro model IL-10 has been shown to synergize with multiple cytokines, including TNF-alpha, in enhancing HIV production.

Methods: Membrane-bound TNF-alpha, TNFR-1 and TNFR-2 surface expression were determined by flow cytometry.

In vitro type-1 and type-2 cytokine production in systemic lupus erythematosus: lack of relationship with clinical disease activity.

Objective: To investigate the relationship between disease activity and in vitro cytokine, soluble(s)CD23 and polyclonal and anti-DNA antibody production by PBMC from patients with active systemic lupus erythematosus (SLE).

Methods: Cytokines, sCD23 and immunoglobulins were estimated by ELISA in unstimulated and polyclonal mitogen-stimulated culture supernatants.

Results: PHA-induced IL-2 and IFN-gamma production were decreased, whereas spontaneous and PHA-induced IL-6 and IL-10 production were increased in cultures of SLE lymphocytes.

Cytokines and soluble receptor changes in the transition from primary to early chronic HIV type 1 infection.

We studied determinants of chronic inflammation and/or immune activation in plasma from patients in the transition from primary to early chronic HIV-1 infection. The following parameters were estimated in seven patients over time: plasma concentrations of soluble CD8 (sCD8), tumor necrosis factor alpha (TNF-alpha), soluble TNF receptor type II (sTNFRII), interleukin 6 (IL-6), soluble IL-6 receptor (sIL6R), IL-10, transforming growth factor beta1 (TGF-beta1), along with CD4- and CD8-positive T cell counts, p24 antigenemia, and clinical evaluation. Results showed that concentrations of sCD8, TNF-alpha, and sTNFRII, and peripheral CD8-positive lymphocyte counts, were significantly increased in patients, compared to HIV-negative controls, and showed a trend toward normal values over time.

In vitro production of type 1 and type 2 cytokines by peripheral blood mononuclear cells from high-risk HIV-negative intravenous drug users.

Objective: To study type 1 and type 2 cytokine patterns in HIV-negative high-risk intravenous drug users (IVDU).

Design: We investigated interleukin (IL)-2, interferon (IFN)-gamma, IL-4, IL-6 and IL-10 production by phytohaemagglutinin (PHA)-stimulated and unstimulated peripheral blood mononuclear cell (PBMC) cultures from HIV-negative high-risk IVDU, HIV-negative controls and HIV-positive subjects.

Methods: Cytokine production was measured in supernatants using enzyme-linked immunosorbent assay (ELISA) in 10 HIV-negative high-risk IVDU, 25 HIV-negative controls, and 12 HIV-positive IVDU.

The effects of thymopentin on the development of SLE-like syndrome in the MRL/lpr-lpr mouse.

Thymopentin (TP-5) is a synthetic pentapeptide that corresponds to the active 32-36 amino acid sequence of the thymic hormone thymopoietin, of which it retains all the immunomodulatory properties. In this study, we have evaluated the effects of long term prophylactic treatment with TP-5 on the clinical, immunological and histological parameters of the SLE-like syndrome that spontaneously occurs in MRL/lpr-lpr (MRL-lpr) mice. TP-5, administered (s.

What is the pathogenetic role of antiphospholipid antibodies?

The association between antiphospholipid antibodies (aPL) and arterial or venous thrombosis, fetal loss and thrombocytopenia defines the so-called "antiphospholipid syndrome" (APS). Despite serial studies in recent years, a clear pathogenetic mechanism(s) has not yet been demonstrated. Several authors have investigated the interaction between aPL and the membranes of blood cells (endothelial cells and platelets) involved in coagulation.

Protection from experimental autoimmune diabetes in the non-obese diabetic mouse with soluble interleukin-1 receptor.

We have evaluated the effects of a treatment with soluble interleukin-1 receptor (sIL-1R) in the accelerated model of autoimmune diabetes induced by cyclophosphamide (CY) in the non-obese diabetic (NOD) mouse. Prior to the CY challenge (350 mgkg body weight), female euglycemic NOD mice were randomly divided into three groups (A-C). Groups B and C were treated daily from 1 day before to 13 days after the CY challenge with sIL-1R at doses of 0.

TH1 and TH2 cytokine production by peripheral blood mononuclear cells from HIV-infected patients.

Objective: To study the TH1-->TH2 cytokine switch, thought to occur during the progression of HIV infection.

Design: We investigated interleukin (IL)-2, interferon (IFN)-gamma, IL-4, IL-6 and IL-10 production by phytohaemagglutinin (PHA)-stimulated and unstimulated peripheral blood mononuclear cell (PBMC) cultures from HIV-negative controls and HIV-positive subjects, stratified according to the Centers for Disease Control and Prevention (CDC) criteria. We correlated the above parameters with markers of disease progression.

Protection from experimental autoimmune thyroiditis in CBA mice with the novel immunosuppressant deoxyspergualin.

The effects of the novel immunosuppressant Deoxyspergualin (DSP) on the development of experimental autoimmune thyroiditis (EAT) in CBA mice were studied. For EAT induction, the mice were immunized with 100 micrograms of porcine thyroglobulin (p Tg) emulsified in CFA on day 0 and in IFA, for boosting, on day 14. Twenty-eight days after primary immunization, histological and serological signs of EAT occurred in control mice treated with PBS which showed marked lymphoid infiltration of the thyroid glands along with increased serum titres of anti-pTg antibodies.

Beta-endorphin content in HIV-infected HuT78 cell line and in peripheral lymphocytes from HIV-positive subjects.

We investigated beta-endorphin (BE) content in an HIV-infected cell line and in peripheral blood mononuclear cells (PBM) from HIV-positive subjects. HIV infection increased BE content in HuT78 cell line compared to uninfected cells. Accordingly, BE content was greater in HIV-positive subjects than in healthy controls, both in fresh PBM and in mitogen-stimulated or unstimulated cultured cells.

Autoantibodies against beta 2-microglobulin-free HLA antigens in AIDS patients.

Serum samples from 88 human immunodeficiency virus (HIV)-positive drug addicts have been investigated for the presence of antibodies to both beta 2-microglobulin (beta 2m)-free and beta 2m-associated HLA class I molecules. Using HIV-negative drug addicts as background control, we found that none of the Centers for Disease Control (CDC) stage II, 9.1% of CDC III, 36.

Toxicological and immune findings in workers exposed to pentachlorophenol (PCP).

Pentachlorophenol (PCP) is a pesticide used worldwide in industrial and domestic applications. Data available on the effects of technical-grade PCP on the immune system are insufficient and equivocal; some data indicate inhibitory effects, whereas others suggest stimulating effects. This study was performed to evaluate toxicological and immune findings in 32 subjects who had prolonged exposure to PCP in a wood factory and in 37 controls.

Prevention of cyclophosphamide-induced diabetes in the NOD/WEHI mouse with deoxyspergualin.

Ten out of 20 (50%) 17-week-old female NOD/WEHI mice developed an acute form of autoimmune diabetes when injected with two large doses of cyclophosphamide (CY), given at 14-day intervals. If these mice were treated under a prophylactic regimen with 2.5 mg/kg body weight per day of the novel immunosuppressant deoxyspergualin (DSP) the onset of diabetes was completely prevented.

In vitro and ex vivo effect of tiaprofenic acid on human peripheral blood mononuclear cells.

The effect of the non-steroidal anti-inflammatory drug (NSAID) tiaprofenic acid on different human immune parameters was investigated in vitro or following in vivo administration in healthy adult volunteers. Results from the in vitro study demonstrated an increased mitogen-induced blastogenesis and interleukin 2 (IL-2) production together with a reduced polyclonal immunoglobulin (Ig) secretion in the presence of the drug. Results from the ex vivo study showed that treatment with tiaprofenic acid had no significant effects on the immune parameters investigated, i.

Enrichment of IgG anti-DNA-producing lymphoblastoid cell lines by antigen-coated immunomagnetic beads.

In this paper we describe the establishment of four anti-DNA-producing lymphoblastoid cell lines (LCL) by Epstein-Barr virus (EBV) infection of peripheral blood B-cells from a patient with systemic lupus erythematosus. The LCL showed a heterogeneous cell composition: the frequencies of cells in active proliferation, cells secreting IgG or IgM, and cells effectively producing IgG or IgM anti-DNA were estimated by limiting dilution analysis. The cells producing anti-DNA antibodies were a small fraction of the whole cell population constituting the LCL.

The effects of deoxyspergualin on the development of diabetes in diabetes-prone BB rats.

The effects of the administration of the recently discovered immunosuppressant 15-Deoxyspergualin (DSP) on the development of insulin-dependent diabetes mellitus (IDDM) in diabetes-prone BB rats were studied. The data show that 2 mg/kg body weight DSP, administered six times a week from the 30th day up to the 105th day of age, significantly reduced the incidence of diabetes in diabetes-prone BB rats as compared with the PBS-injected controls. The drug was also able to reduce the signs of pancreatic insulitis and the percentages of W3/25+ and OX6+ splenocytes.