Interleukin-1 secretion by lipopolysaccharide-stimulated alveolar macrophages. Relationships to cell numbers--influence of smoking habits.

Interleukin-1 (IL-1) release by alveolar macrophages (AMs) from 29 patients with primary bronchogenic carcinoma, lung metastases, acute pneumonitis, and chronic infection was evaluated in response to a standard stimulus, lipopolysaccharide (LPS). The results were compared to those of AMs from normal smokers or nonsmokers (volunteers). AMs derived from healthy smokers secreted significantly more IL-1 than AMs from nonsmokers.

Imuthiol influences on cytotoxic T cells and NK activity in +/+ and athymic nude BALB/c mice.

The effects of imuthiol (sodium ditiocarb, DTC) on the expression of cytotoxic responses (CTL) and natural killer (NK) activity were evaluated in aged and young euthymic mice, and in nu/nu BALB/c mice. Imuthiol generated CTL and concomitantly reduced NK activity in nu/nu mice, suggesting that the agent can generate T cells in athymic nude animals. Treatment for up to 4 months augmented spleen NK and CTL activities in young or aged euthymic mice, but the generation of CTL in old animals was increased by long-term treatments better than by a single injection.

Sodium diethyldithiocarbamate protects against the MPTP-induced inhibition of immune responses in mice.

The effects of 1-methyl-4-phenyl - 1,2,3,6-tetrahydropyridine (MPTP) on immune parameters, and the restorative influence of sodium diethyldithiocarbamate (DTC) or deprenyl were evaluated in mice. The concentrations of dopamine (DA), 3-methoxytyramine (3-MT), 3-4-dihydroxyphenyl acetic acid (DOPAC), and homovanillic acid (HVA), were concomitantly measured in the striatum. MPTP depressed T-cell responses.

Immunologic indices in myelodysplastic syndromes.

Immunocompetence was evaluated in 36 untreated and noninfected patients affected with myelodysplastic syndromes (MDS). T-cell number and activity were evaluated by counts of total T-cells and T-lymphocyte subsets, and by measure of DNA synthesis in response to phytohemagglutinin and Concanavalin A. B-cells were evaluated as surface immunoglobulin- (SIg+) bearing cells and by serum immunoglobulin levels.

The cortex regulates the immune system and the activities of a T-cell specific immunopotentiator.

Evidence has accumulated to demonstrate important bidirectional communications between the nervous and immune systems. The anatomic pathways of communication include the commitment of different midbrain areas to regulation of immunologic functions. Neuropeptides appear as critical mediators of neuroregulation of function of diverse immunocompetent cells.

Brain neocortex and imuthiol regulate the expression of MHC antigens on mouse T lymphocytes.

The induction of T-cell responses involves the recognition of extrinsic antigens in association with antigens of the major histocompatibility complex (MHC). The present results demonstrate that the lateralized control exerted by the brain neocortex on T-cell activities extends to the expression of MHC antigens, yet differently on spleen or lymph node T cells. This study also shows that the neocortex influences the changes induced by an immunopotentiator, sodium diethyldithiocarbamate (imuthiol), on the MHC antigen content on mouse T cell-surface.

Immunopharmacology and immunotoxicity of zinc diethyldithiocarbamate.

Zinc is essential for the functions of the immune system, and sodium diethyldithiocarbamate (imuthiol) restores and regulates the numbers and activities of cells of the T-cell lineage. The combination of both elements was therefore tested for immune enhancement and immunotoxicity. The data presented herein show that the administration of zinc diethyldithiocarbamate was devoid of immunoenhancing influence on the responses to T-cell mitogens, and exerted a cytocidal effect on spleen lymphocytes.

Asymmetrical involvement of the cerebral neocortex on the response to an immunopotentiator, sodium diethyldithiocarbamate.

We have previously shown that the neocortex in mice has a lateralized influence on the immune system. A partial left or bilateral neocortical lesion selectively decreases spleen T-cell numbers and function, natural killer and (NK) activity, but a right neocortical lesion do not affect NK activity, and increases T-cell numbers and T-cell-mediated events. Here we report that the immunopotentiating activity of sodium diethyldithiocarbamate (Imuthiol), a compound that selectively increases T-cell numbers and activities, is dependent on an intact neocortex.

Fate and distribution of radioactive sodium diethyldithiocarbamate (Imuthiol) in the mouse.

The distribution of 35S in mouse tissues has been investigated by radioactivity counts and by autoradiography after the intravenous injection of 35S-labeled imuthiol (sodium diethyldithiocarbamate). Radioactive Imuthiol is selectively localized on liver, thymus and brain neocortex, most likely as the methyl ester, within minutes after dosing. Lung or white brain matter did not fix the labeled thiol.

The ten commandments for immunotherapeutic drugs at the example of sulfur-containing agents.

Immunotherapeutic agents (IMT) are intended to restore or reequilibrate a faltering immune system. Levamisole was the first chemically defined IMT endowed with immunomodulatory effects. In order to clarify the mechanisms of its ambivalent activities, thiocompounds were tested for their ability to modify immune responses.

Influences of sodium diethyldithiocarbamate, DTC (imuthiolR) on T cell defective responses of aged BALB/c mice.

The effect of chronic imuthiol treatment, 25 mg/kg weekly for 4 months initiated at the age of 12 months, on T-cell functions of aged female BALB/c mice was investigated. Imuthiol restored to normal value the impaired response to Concanavalin A (Con A) and enhanced the proliferative response to phytohemagglutinin (PHA). Impaired cytotoxic T-cell activity (CTL), was restored near to the value of young controls by imuthiol.

Clinical characterization of imuthiol.

Imuthiol is a nontoxic agent recruting and regulating T cells. Phase III studies in chronic bronchitis and bronchiectasis showed that immune functions were restored to normal, or near normal values. Cure was obtained in rheumatoid arthritis, tuberculosis and chronic infections in the elderly.

Characterization of immunotherapeutic agents: the example of imuthiol.

Immunotherapeutic (IMT) agents are intended to restore or reequilibrate a faltering immune system. These aims will be attained provided the agent fulfills minimum requirements: in vivo defined activities; lack of suppressive, sensitizing, or autoimmunity-inducing influence; no immunotoxicity and carcinogenicity. Known chemical structure, analytical procedure, toxicology and pharmacology are also prerequisites.

Disseminated aspergillosis in a patient with bronchiectasis. A 15-month clinical and immunological follow-up.

We report a case of disseminated aspergillosis involving both lung and brain in an adult female patient affected with bronchiectasis. Immunological follow-up was conducted before the clinical diagnosis and during the illness and revealed an excessively high helper-inducer/cytotoxic-suppressor (T4/T8) ratio. Peripheral granulocyte function was normal.

Early changes in immune parameters induced by an acute nonantigenic inflammation in mouse: influence of imuthiol.

Calcium pyrophosphate (CaPP)-induced pleurisy, may represent one of the simplest expressions of inflammation in that the irritant is a non-diffusible, non-antigenic and non-pyrogenic agent. Spleen or lymph node T or B cell numbers and activities, as well as NK activity, were modified at distance by CaPP-pleurisy. An intense increase in blood polymorphonuclear cells was also triggered by the inflammatory process.

Favorable influences of imuthiol on mouse reproduction and immune system of offspring.

A physiological immature immune system in newborns is a common feature frequently associated with increased susceptibility to infections. The properties of imuthiol (purified sodium diethyldithiocarbamate), an agent specifically active on the T-cell lineage, and virtually devoid of toxicity for man or animals, encouraged us to determine whether imuthiol administered to the dams could increase the immune capability of offspring without altering fecundability and birth rate. Experiments performed either in histocompatible or histoincompatible mating systems, show that chronic administration of imuthiol prior to mating and/or during pregnancy stimulated newborn mice to increased T-cell-dependent responses, without altering birth rates and growth curves in progenies.

Sodium diethyldithiocarbamate influences the early immunological changes evoked by an acute non-antigenic inflammation process.

Calcium pyrophosphate (CaPp) produces an acute local inflammatory process when administered intra-pleurally. It is the simplest model of an inflammation uncomplicated by pharmacological properties of the agent or the presence of an antigen. Spleen or lymph-node T- or B-cell numbers and activities, including NK activity, are modified within 2 h under these conditions.

The generation and regulation of human T lymphocytes by Imuthiol. Evidence from an in vitro differentiation induction system.

In vitro long term induction of human peripheral blood lymphocytes by sodium diethyldithiocarbamate, DTC (Imuthiol) enhanced the expression of OKT and HLA-DR phenotypic determinants. A population of T-B-DR+ cells was recruited from the null cell population. The increase in OKT+ cells, but not the enhanced HLA-DR expression appeared to be macrophage dependent.