Immunomodulatory peptides

Thymosin is an immunomodulatory peptide produced by the thymus gland and other cells. Thymosin alfa 1, a 28-amino acid peptide, is one member of the family of thymosins that collectively appear to influence a variety of regulatory and counter-regulatory functions in terms of T-cell maturation and antigen recognition, stimulation of native interferons and cytokines such as interleukin-2, and activity of natural killer cell-mediated cytotoxicity. In some countries it is approved as an adjuvant for influenza vaccine or as a treatment for chronic hepatitis B and, in combination with interferon for hepatitis C. Thymosin alfa 1 has been used with some success to treat children with the severe form of Di-George Syndrome. 

CWTKSYiOpPKPGFVR (disulfide bond C -G ), an immunomodulatory peptide isolated from the skin of the Northern Leopard frog (Ranapipiens). The name PLR reflects the N- and C-terminal residues. 

Peptides with different bioactivities have been identified in many fermented milks, such as sour milk, yogurt, kefir and dahi, as reviewed by Fitzgerald and Murray (2006), Korhonen (2009) and Hernandez-Ledesma et al. (2011). In addition to anti-hypertensive peptides, casein phosphopetides, antimicrobial, antioxidative and immunomodulatory peptides have been found depending on the origin of milk, dairy cultures and technology applied in production. 

Gauthier, S.F., Pouliot, Y., Saint-Sauveur, D., 2006. Immunomodulatory peptides obtained by the enzymatic hydrolysis of whey proteins. International Dairy Journal 16, 1315—1323. Ghilzai, M., June 2004. Advances in the delivery of large-size drug molecules. Innovations in Pharmaceutical Technology 103—108. 

Host Defense Peptides Bridging Antimicrobial and Immunomodulatory Activities... 

Figure 1 Cartoon representation of the human cathelicidin hCAPI 8. The amino acid residues that define each of the three hCAP18 domains have been added. The sequence of LL-37, the host defense peptide derived from hCAP18, is found in the inset. Structure-activity relationship studies have identified regions within the peptide that are necessary for both antimicrobial and immunomodulatory activities.

Despite the unresolved issues regarding the relative importance and the exact physiological roles of the direct antimicrobial and immunomodulatory activities of host defense peptides, there is overwhelming evidence that the peptides play a pivotal role in the mammalian innate immune response. Human disease... 

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. 

Table 1 Immunomodulatory activities and cellular locations of a subset of natural host defense peptides... 

Peptide Origin Cellular location Immunomodulatory activity Proposed receptors... 

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