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      Modulation of Delayed-Type Hypersensitivity Responses in Hairless Guinea Pigs by Peptides Derived from Enkephalin

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          Although opioid peptides such as methionine (met)-enkephalin have been previously shown to enhance or suppress immune responses, few studies in animal models have addressed the immunomodulatory activity of their metabolic derivatives. Hairless (IAF/HA-HO) guinea pigs immunized with Freund’s complete adjuvant containing Mycobacterium tuberculosis and repeatedly skin tested with purified protein derivative of tuberculin (PPD) display high levels of stable delayed-type hypersensitivity (DTH) to PPD. Met-enkephalin (YGGFM) and two of its metabolites (YGG, YG) enhanced and accelerated PPD-elicited DTH inflammatory reactions when injected together with elicitor in these animals. At 24 h, 5 × 10<sup>–3</sup> pmol met-enkephalin significantly enhanced DTH responses by 30% over PPD alone, while 5 × 10<sup>–5</sup> pmol of YGG and 5 × 10<sup>–9</sup> pmol of YG significantly enhanced these responses by 62 and 32%, respectively. At much higher doses (5 × 10<sup>3</sup> pmol), met-enkephalin and its metabolites significantly suppressed DTH reactions by 25–32%. Tyrosine and glycine had no effect on PPD-elicited DTH. All DTH reactions (control, enhanced, suppressed) displayed typical perivascular mononuclear cell infiltrates. We conclude that the immunoactivity of met-enkephalin resides in its first two amino acids and suggest that cleavage of enkephalin molecules to YG occurs in serum and/or on the cell surface.

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          Most cited references 11

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          Pathogen-specific regulatory T cells provoke a shift in the Th1/Th2 paradigm in immunity to infectious diseases.

          Current dogma suggests that immunity to infection is controlled by distinct type 1 (Th1) and type 2 (Th2) subpopulations of T cells discriminated on the basis of cytokine secretion and function. However, a further subtype of T cells, with immunosuppressive function and cytokine profiles distinct from either Th1 or Th2 T cells, termed regulatory T (Tr) cells has been described. Although considered to have a role in the maintenance of self-tolerance, recent studies suggest that Tr cells can be induced against bacterial, viral and parasite antigens in vivo and might prevent infection-induced immunopathology or prolong pathogen persistence by suppressing protective Th1 responses. These observations have significant implications for our understanding of the role of T cells in immunity to infectious diseases and for the development of new therapies for immune-mediated disorders.
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            Stimulation of human peripheral blood lymphocytes by bioactive peptides derived from bovine milk proteins.

             H Meisel,  H Kayser (1996)
            The in vitro modulation of the proliferation of human peripheral blood lymphocytes by different synthetic peptides derived from milk proteins was investigated. Therefore, proliferation changes were followed up after incorporation of BrdU into the DNA, and the influence on protein biosynthesis was measured using the [3H]leucine incorporation test. Tyr-Gly and Tyr-Gly-Gly significantly enhanced (maximal 90 and 35%, respectively) the proliferation of PBL. For beta-casomorphin-7 and beta-casomorphin-10,lymphocyte proliferation was suppressed at lower concentrations, but stimulated at higher concentrations (> or = 10(-7) mol/l). Protein synthesis was stimulated (maxima at 25%) only with Tyr-Gly and Tyr-Gly-Gly. The findings point to a need for further studies on the possible function of peptides derived from milk proteins as orally bioavailable immunopotentiatory compounds.
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              Th1-Th2 Paradigm: Insights from Leprosy


                Author and article information

                S. Karger AG
                April 2004
                14 April 2004
                : 11
                : 3
                : 141-148
                aDepartment of Biological Sciences, Alcorn State University, Alcorn State, Miss., bDepartment of Dermatology and Pathology, SUNY-Downstate Medical Center, Brooklyn, N.Y., and cDepartment of Pathology, New York Medical College, Valhalla, N.Y., USA
                76763 Neuroimmunomodulation 2004;11:141–148
                © 2004 S. Karger AG, Basel

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                Page count
                Figures: 4, References: 33, Pages: 8
                Original Paper


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