Immunomodulation by Opioid Peptidomimetic Compound

Abstract

Objective: As a follow-up to our earlier studies on immunomodulation with opioid peptides, we synthesized and evaluated immunomodulatory activity of four peptidomimetic compounds, i.e. Tyr-NH-C(Me)₂-CH₂-O-Phe-NH₂(1), Tyr-NH-C₆H₅-(o)-CH₂-CH₂-O-Phe-NH₂ (2), Tyr-NH-CH₂-CH₂-O-Phe-NH₂ (3) and Tyr-NH-CH(D-Et)-CH₂-O-Phe-NH₂ (4). Methods: These compounds were synthesized in solution phase and evaluated for their immunomodulatory properties in vitro by mixed lymphocyte reaction (MLR), proliferation of opioid receptor-expressing cells, production of tumor necrosis factor-α (TNF-α) and nitric oxide. Results: This study shows the immunosuppressive potential of synthetic peptidomimetic compound 3. This compound inhibited two-way MLR and suppressed the proliferation of the µ-opioid receptor expressing human embryonic kidney cells HEK 293 in vitro. Inhibition of MLR by compound 3 was reversed by naloxone (opioid receptor antagonist) and β-funaltrexamine hydrochloride (µ-opioid receptor antagonist). The immunosuppressive effect of compound 3 was further demonstrated by inhibition of TNF-α and nitric oxide production in lipopolysaccharide-stimulated human PBMCs and mouse macrophage cells RAW 264.7, respectively. Conclusion: These observations suggest that compound 3 inhibits MLR through µ-opioid receptor present on cells.

Tocopherol succinate: A promising radiation countermeasure

“…We have previously evaluated several immunomodulators for cytokine induction but TS stimulates G-CSF to greater extents than any other agent [38][39][40][41][42][43][44][45]. This study also demonstrates an increase in message of G-CSF in bone marrow cells by sc administration of TS.…”

Mechanisms of postoperative ileus

“…Opioids are known to alter immune function through numerous mechanisms by binding to specific opioid receptors on leucocytes 59–63 . Interestingly, however, diametrically opposite results are encountered when delineating the effects of individual opioid receptors.…”

“…Opioids are known to alter immune function through numerous mechanisms by binding to specific opioid receptors on leucocytes. [59][60][61][62][63] Interestingly, however, diametrically opposite results are encountered when delineating the effects of individual opioid receptors. In general, l-opioid agonists are reported to be primarily immunosuppressive, while d-opioid agonists appear to be immuno-enhancing.…”

Peptides and Peptidomimetics as Immunomodulators

“…In this review article, we will cover therapies for major autoimmune diseases such as RA, MS and SLE employing peptides and peptidomimetics. There are reports of opioid peptidomimetics that can be used for immunomodulation [35]. …”