Immunomodulating peptides

Wagle, J. R., Ansevin, A. T., Dessens, S. E., and Nishioka, K., Specific translocation of tuftsin (Thr-Lys-Pro-Arg), a natural immunomodulating peptide, into the nuclei of human monocytes, Biochem. Biophys. Res. Commun., 159, 1147, 1989. 

Results from testing combinatorial libraries will support the design of cocktails of peptides applicable in prophylactic or therapeutic tumor vaccination or the construction of immunomodulating peptides for therapy of autoimmune diseases. Peptide libraries are also one of the most promising tools in the development of therapeutic approaches based on the actual status of an individuals immune response. 

Immunomodulating peptides. Enzymatic digests of human caseins contain immunomodulating peptides which stimulate the phagocytic activity of human macrophages in vitro and exert a protective effect in vivo in mice against Klebsiella pneumoniae infection. Two of the peptides were characterized as H.Val.Glu.Pro.Ile.Pro.Tyr (/6-CN f54-59) and H.Gly.Leu.Phe (origin not identified). 

Reithmeier, H., Gopferich, A., and Herrmann, L, Preparation and characterization of lipid microparticles containing thymocartin, an immunomodulating peptide. Proceedings of the International Symposium on Controlled Release of Bioactive Materials,Yol. 26, p. 681,1999. 

Bleomycin and cyclosporine are the two economically most important streptomycete peptide antibiotics used as antitumor agents and immunomodulators, although dactinomycin is important medically for several tumors (see Chemotherapeutics, anticancer Immunotherapeutic agents). 

Caryophyllidae are an interesting source of oligosaccharides and peptides with potential anti-inflammatory and/or immunomodulating effect. These polar compounds might for instance explain the fact that the fresh juice expressed from Aerva lanata (L.) Juss. (Amaranthaceae) inhibits carrageenan-induced edema in rodent. Note that the seeds of Gomphrena species inhibit the formation of IL-6 by osteoblastic cells (MC3T3-E10) without cytotoxicity in vitro. Such property could be useful for the treatment of chronic rheumatoid arthritis, infection, and cancer. In the Lauraceae, trans-cinnamal-dehyde from Cinnamomum cassia (Lauraceae, order Laurales) inhibits in vitro the... 

Brynestad K, et al. Influence of peptide acylation, liposome incorporation, and synthetic immunomodulators on the immunogenicity of a 1-23 peptide of glycoprotein D of herpes simplex virus implications for subunit vaccines. J Virol 1990 64 680. 

Recently, the activities of host defense peptides related to the resolution of infection have been suggested to result in part from nondirect antimicrobial activities. It has been postulated that immunomodulation may represent the primary action of these peptides in vivo as the immunomodulatory activities are retained under physiological conditions in contrast to the direct antimicrobial activities of most natural mammalian host defense peptides. These immunomodulatory activities include, but are not limited to, direct chemotactic activity, induction of chemokines and other immune mediators, stimulation of leukocyte degranulation and other microbicidal activities, effects on leukocyte and epithelial cell survival and apoptosis, stimulation of epithelial and endothelial cell proliferation, promotion of wound healing and angiogenesis, antiendotoxic and anti-inflammatory activities, and adjuvant fiinctions. These will be described in detail in the following sections and a summary is found in Table 1. 

Further, acidic peptide fractions from Atlantic cod hydrolysate have shown strong immunostimulatory effects, and treatment of these peptides has stimulated the oxidative burst of Atlantic salmon leucocytes (Gildberg et al., 1996). Basically, immunomodulators that enhance the production of oxygen metabolites in macrophages that are responsible for these oxygen metabolites determine the oxidative burst. Oxidative burst reactions are of major importance for the bactericidal power of phagocytes. 

The discovery of a multitude of naturally occurring, bioactive peptides has generated a rich source of pharmacophores from which medicinal chemists are developing new useful therapeutic drugs. After binding to an enzyme, or a membrane receptor, peptide-based inhibitors, neurotransmitters, immunomodulators, and hormones influence cell-to-cell communications and control a variety of vital functions such as metabolism, immune defense, digestion, respiration, sensitivity to pain, reproduction, and behavior. 

Raz, I., Elias, D., Avron, A., Tamir, M., Metzger, M and Cohen, I.R. (2001) Betacell function in new-onset type 1 diabetes and immunomodulation with a heat-shock protein peptide (DiaPep277) a randomised, double-blind, phase II trial. Lancet 24, 1749-1753. 

The direct effects opioid and opioidlike peptides exhibit on cells of the immune system is both varied and, in some instances, contradictory, depending on which receptor subtype is being studied. Mu and kappa receptors generally affect immunofunction in a suppressive manner, where delta receptors tend to express immunostimulation [82-85]. However, selected delta antagonists have shown to elicit suppressive effects on B-cell proliferation, NK cell activity, and T-helper cell cytokine production [86]. The alteration of leukocyte function via opioid receptors will be discussed highlighting specific cell subtype immunomodulation. Endorphin shows a inhibitory effect on splenocyte proliferation through central and peripheral autocrine/paracrine pathways [87]. 

Ca carrier, immunomodulation, anticarcinogenic, precursor for bioactive peptides Walzem et al. (2002)... 

Fiat, A.-M., Migliore-Samour, D., Jolles, P., Drouet, L., Collier, C., and Caen, J. 1993. Biologically active peptides from milk proteins with emphasis on two examples concerning antithrombotic and immunomodulating activities. J. Dairy Sci. 76, 301—310. 

Migliore-Samour, D., Floc h, F., and Jolles, P. 1989. Biologically active casein peptides implicated in immunomodulation. J. Dairy Res. 56, 357—362. 

Takahashi, M., Moriguchi, S., Yoshikawa, M., and Sasaki, R. 1994. Isolation and characterization of oryzatensin, a novel bioactive peptide with ileum-contracting and immunomodulating activities derived from rice albumin. Biochem. Mol. Biol. Int. 33, 1151 — 1158. 

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