Immunostimulators

The macrophage appears to play a major role in initiating the cellular immune system with the production and secretion of soluble factors (monokines) which regulate various cellular components. These monokines, along with lymphokines (lymphocyte secreted cell regulators) and specific chemicals comprise the bulk of the fist of biologic response modifiers. 

As reviewed by Yamamoto (1985) and Beato (1989) steroid hormones influence gene expression at essentially all known levels of regulation. 

In certain cases, steroid hormones were converted into corresponding radical intermediates in either enzymatic or non-enzymatic systems (Ko-DADMA et al. 1997). Although detection of the free radicals was limited to oestrogens, evidence suggests that glucocorticoids as well as androgens may also share the physiological formation of free radicals. 

In general, the concentrations of hormones needed to inhibit peroxidation in vitro seem much 

Phagocytosis of Staphylococcus aureus by macrophages elicited in rafcfczfsbyintrapleural application of Liebig s meat extract plus carboxymethylcellu-lose was 50% enhanced when the animals had been injected subcutaneously with 0.2 mg cortisone acetate per kg body weightxday (Crabbe 1956). 

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The active immunotherapeutic approach is specific and based on the premise that tumor antigens are immunogenic and the host is sufficientiy immunocompetent to mount an effective immune response to an autologous tumor. Theoretically, a weak or suppressed host immune system that had allowed the formation of a tumor may be overridden by active immunization or immunostimulation. In practice, vaccines composed of so-called autologous tumor extracts have been used to treat patients with malignant melanoma (73), and purified melanoma tumor-associated antigens have been used to ehcit antibody responses in melanoma patients (74). 

Not only is TCDO a potent therapeutic agent in acute radiation syndrome, but treatment using TCDO from days 4—11 after TBI increases the survival rate in rats for up to one year, protects against the development of late GI ulcers, and also reduces the development of y-ray-induced leukemias and malignant epitheHal tumors, but not sarcomas (202). The anticarcinogenic effect of TCDO maybe related to the inhibition of PGs, which promote carcinogenesis, or to immunostimulation, which may result in a more effective elimination of malignant cells. 

In 1971, levamisole, an anthelmintic compound widely used in catde and swine, was shown to improve the effects of an experimental Brucella abortus vaccine in mice. Since that time, the veterinarians and physicians have explored the effects of levamisole in such diverse areas as arthritis, lupus erythematosis, cancer therapy, respiratory diseases, Newcastle disease, foot-and-mouth disease, mastitis, and vaccine potentiation. Although the exact mechanism of action has as yet not been deterrnined there is substantial evidence that, under defined circumstances, levamisole can augment the animal s natural immune response (9). New immunostimulants include Staph Ijysate acemannon, NLAB-31. 

For many of the drugs, however, the active constituents are not (yet) known the examination of their activity is thus often rendered more difficult in that experience of its administration over a long period of time is required. In these cases, it is often said that the drug concerned stimulates the body s own defence mechanisms formerly, the administration of such drugs was called nonspecific stimulant therapy, nowadays the concept of immunostimulation is used or paramunity inducers [I-6]. 

Methyl-A -(3-methoxyphenyl)-l//-l,2,3-triazolo[5,4-/]quinoline-9-amine was prepared and tested as an immunostimulant (93MI2). 

Polysaccharides isolated from the seeds of C. chinensis have effects both as immunostimulants and as antioxidants. The polysaccharide CS-A-3-/1 has a backbone of a-D-l,4-hnked GalpA and /1-L-1,2-Rhap imits with branches at C-4 of the Rhap residues and at C-3 of GalpA residues that are composed of an arabinogalactan and glucobiose. The Ara/ imits are terminal and 1,5-... 

H. Umezawa hoped to obtain immunostimulants from microbes, because, in cancer patients, the immune response is lowered. In 1972, H. Umezawa, T. Takeuchi, and M. Ishizuka (now Vice-Director of the Institute for Chemotherapy, a branch of IMC) found that the administration in mice of a small dose of diketocoriolin B, an oxidation derivative of the antitumor antibiotic coriolin B (1971), increases the number of mouse-spleen cells... 

Wagner et al. obtained immunostimulating pectic polysaccharides from plant cell culture of Echinacea purpurea [5]. From the extracellular polysaccharide... 

A considerable amount of extracellular polysaccharides is produced in the process of cultivation of certain plant suspension cultures and the spent culture medium has proved to be an accessible source for their production (1-3). The interest in investigating these extracellular polysaccharides has been quite strong over the past 10-15 years, motivated by their biological activity (4,5). Plants of the Asteraceae family, as well as their cell cultures, have been established to contain polysaccharides with immunostimulating activity (1-6). The object of our research was Helianthus annuus 1805 cell culture (Asteraceae), which according to the preliminary investigation produces a considerable amount of exopolysaccharides. 

The results of the biological investigation showed that polysaccharide fraction I had a distinct immunostimulating activity. 

Immunological tests indicated that fraction 1, obtaned by gel chromatography had an immunostimulating activity. It induced migration of peritoneal-exudative cells, respectively peritoneal macrophages into the peritoneal cavity of experimental animals. These cells are with high bactericidic metabolitic activity. 

Vaccination to induce an adaptive immune response is expected for a broad range of infectious diseases and cancers. Traditional vaccines are mainly composed of live attenuated viruses, whole inactivated pathogens, or inactivated bacterial toxins. In general, these approaches have been successful for developing vaccines that can induce an immune response based on antigen-specific antibody and cytotoxic T lymphocyte (CTL) responses, which kill host cells infected with intracellular organisms (Fig. 1) [1,2], One of the most important current issues in vaccinology is the need for new adjuvants (immunostimulants) and delivery systems. Many of the vaccines currently in development are based on purified subunits, recombinant... 

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