Immuno stimulation

D. Tracey and K. Richard, "Mechanisms of Immuno stimulation by Pyrimidiuones," iu Immunopharmacology of Infectious Diseases Uaccine Mdjuvants and Modulators of Non-specific Resistance, Alan R. Liss, Inc., 1987, pp. 279—289. 

We modified polyanionic polymers by use of a grafting reaction of hydrophobic groups onto the polymers. After an extensive evaluation for the affinity of the hy-drophobically modified (hydrophobized) polymers to cell membrane, the immuno-stimulating activity of polymers was investigated by in vitro or ex vivo experiments. Consequently, the increased biological activity was found in the hydrophobized polymer, indicating that... 

Based on these observations in Figs. 8 and 9, it is suggested that the hydrophobic group modification (hy-drophobization) is an effective method for improving the immuno-stimulating activity of polyanionic polymers. 

For additional evaluation of the effect of hydrophobization and the molecular weight of the polymers on the biological immuno-stimulating activity, we investigated the ex vivo cytokine (interIeukin-6 [IL-6], and tumor necrosis factor [TNFj-inducing activity from human peripheral whole blood cells of hydrophobized polymers by use of fractionated poly(M A-CDA) with narrow poly-dispersity. Since this assay uses the intact human cells, it shows more accurate results than in vitro assay using cultured cell line [25]. 

Immunocyanin is an effective medicine for the treatment of urinary bladder carcinoma. It is derived from a sea snail protein. The instillation of immunocyanin into the bladder results in a marked immuno-stimulation of macrophages and hence a specific immune response against mmour cells that are still in the bladder after cancer therapy. 

Jeon, Y. J. and Kim, S. K. (2001). Potential immuno-stimulating effect of antitumoral fraction of chitosan oligosaccharides. J. Chitin Chitosan 6,163-167. 

Proksch, A. and Wagner, H. 1987. Structural analysis of a 4-O-methyl-glucuronoarabinoxylan with immuno-stimulating activity from Echinacea purpurea. Phytochemistry 26, 1989-1993. 

There are many published therapeutic uses of the thyme oils. Linalool CT, with very low phenol content, is attributed properties such as reviving, strengthening nerves and aiding concentration by stimulation of the cerebral regions of the brain. It is considered to be an immuno-stimulant and safe for use with children. The high ester content also contributes to its application as an antispasmodic for dry coughs. 

In contrast the thymol CT varies widely with the alcoholic CTs in both olfactory and therapeutic properties. Thymol CT is also attributed immuno-stimulant action but it is strongly antiseptic and is used for infectious conditions like colds, coughs and bronchitis. It is also recommended for its warming analgesic properties for treatment of rheumatism, arthritis and sciatica. It stimulates the digestive and cardiovascular systems and may help raise the blood pressure. 

Immunotherapy Interferon-alpha has an antiproliferative effect on tumour cells. Previous studies, however, have shown no success in HCC, not even when IFN was combined with cytostatics. In order to improve the severely weakened immune system of tumour patients, immuno-stimulants (e.g. autologous lymphocyte infusion, thy-mostimulin) were used. (137) The incorporation of lipo-... 

Echinacea purpura (Echinacea) used as an anti-inflammatory and immuno-stimulant ... 

The peptidoglycan and fragments of it exhibit pronounced immno-stimulatory properties. The minimal structure required for the immuno-stimulation is a muramyl dipeptide (MDP, A -acetylmuramyl-L-Ala-y-D-Gln). Many investigations were directed towards the synthesis of derivatives of MDP. Fukase et al. have synthesized several MDP derivatives, as well as polymeric MPP derivative (compounds 24-29) 14, 15) in these efforts. 

Immunostimulation is defined as the nonspecific enhancement of cellular and/or humoral immune reactions. Immuno-stimulants do not produce antibodies but do lead to changes in the immune system such as increased formation of granulocytes and macrophages, increased phagocytic activity as well as the following ... 

USA interferon, gamma-lb interferon Actimmune Immukin, Imukin 1 Natural sourced Immuno- stimulant... 

USA pegademase bovine enzyme Adagen Reaction product of recombinant adenosine deaminase with succinic anhydride and subsequent esterification with polyethylene glycol monomethyl ether Immuno- stimulant... 

Gribble EJ, Sivakumar PV, Ponce RA, Hughes SD. Toxicity as a result of immuno-stimulation by biologies. Expert Opin Drug Metab Toxicol 2007 3(2) 209-234. 

Szab6, C., Southan, G. J., Wood, E., Thiemermann, C., and Vane, J. R. (1994b). Spermine inhibits the production of nitric oxide in immuno-stimulated J774.2 macrophages Requirement of a serum factor. Br. J. Pharmacol. 112, 355-356. 

Szabo C, Salzman AL. Endogenous peroxynitrite is involved in the inhibition of mitochondrial respiration in immuno-stimulated J774.2 macrophages. Biochem Biophys Res Commun 1995 209 739-43. 

Other immuno-stimulants were isolated by Umezawa and his colleagues in Tokyo from microbial sources. These substances, which strongly inhibited peptidases, could also activate T-cell immune responses in mammals. One of them, bestatin, has found clinical use in those types of cancer where immune-repression can be demonstrated. Bestatin is 3-amino-4-phenyl-2-hydroxy-butyryl-leucine, and is non-toxic to Man (Carter, Sakurai and Umezawa, 1981). 

Many attempts have been made to find immuno-stimulators among existing synthetic substances. Levamisole (5.5), one of the best of these, acts as a thymomimetic in mice. Thus, it can restore poorly functioning phagocytes and T-lymphocytes and induce T-cell differentiation, but it does not increase T-cell immune responses above their normal level. Moreover, it has no effect on B-lymphocytes. It readily breaks down in the body to 2-oxo-l-mercaptoethyl-4-phenylimidazole (5.7) which has all the properties of levamisole. Thus levamisole seems to be the pro-drug for OMPI (5.7) which acts directly on lymphocytes. OMPI also stimulates secretion of a factor, thought to be thymus hormone, which, too, stimulates lymphocytes (Symoens et al., 1979). 

As can happen with immuno-stimulants, levamisole is immuno-suppressive in larger doses. The latter property suggested the clinical trials, which are taking place in Belgium, for the treatment of arthritis. 

The in vitro human whole blood assay and the outbred mouse are considered binary (yes/no) hazard identification tools in lead optimization screening for compound selection. In our experience to date, chemically modified conjugate siRNAs do not provoke acute pro-inflammatory effects in subsequent rodent or nonrodent studies or in clinical trials if they test negative in these two assays. Lacking positive controls, it is not yet feasible to assess whether the immuno-stimulation screening during lead optimization is predictive or relevant for human outcomes. 

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