T lymphocyte proliferation is suppressed by the opioid growth factor ([Met5]-enkephalin)–opioid growth factor receptor axis: Implication for the treatment of autoimmune diseases

Synergistic effect of methionine encephalin (MENK) combined with pidotimod(PTD) on the maturation of murine dendritic cells (DCs)

“…28,29 One native opioid peptide, MENK, has emerged as a modulator on several immunological functions both in vitro and in vivo such as enhancing the proliferation of peripheral blood lymphocytes and splenocytes. 30 MENK possesses bilateral regulation on immune cells, which means that MENK at higher concentrations such as 10 -6 M or lower concentrations such as 10 -18 M will delay immune cell growth and the possible mechanism is MENK can interact with OGFr to upregulate cyclin-dependent kinase inhibitory (CKI) pathways and markedly delay the G 1 /S phase of the cell cycle. [31][32][33][34] However, MENK at a range of physiological concentrations between 10 -11 and 10 -15 M will enhance immune cell growth.…”

Targeting opioid signaling in Crohn’s disease: new therapeutic pathways

“…CD and other autoimmune diseases are widely thought to be related to T-cell-mediated immunity, although there is evidence for humoral immunity in the disease process by an antigen-driven B-cell response. T and B cells depend on proliferation for response and OGF depresses T-and B-cell proliferation by an OGFr-dependent inhibitory pathway involving p16 and p21 [21,22]. As added evidence that opioid antagonists do not have a direct effect on immune response, continuous opioid receptor blockade by NTX has no effect on T-or B-cell proliferation.…”

“…This may be due in large part because only small amounts of preproenkephalin-derived peptides, which require dibasic cleavage for formation of smaller peptides (e.g., OGF) and are the opioid-active forms, have been recorded in T lymphocytes. However, the OGFr has been documented in T and B cells, and this peptide is fully capable of inhibiting cell proliferation through p16 and p21 cyclin-dependent inhibitory kinase pathways [21,22].…”

A New Biotherapeutic Approach for the Treatment of Multiple Sclerosis

“…Direct administration of this non-toxic, pentapeptide also minimized progression of progressive EAE [24] when given at the time of disease induction or at the time of established disease [25], a more clinically relevant model. The specific targets and pathways that OGF uses to repress cell division have been outlined [20][21][22][23][24][25][26][27][28], and many in vitro (tissue culture) reports on normal or cancer cell lines document that OGF acts directly on the OGFr to inhibit cell proliferation [15,16]. The action is reversible, non-apoptotic, and independent of the immune system, other than inhibiting inflammatory T cells following immunization [27][28][29].…”

“…The specific targets and pathways that OGF uses to repress cell division have been outlined [20][21][22][23][24][25][26][27][28], and many in vitro (tissue culture) reports on normal or cancer cell lines document that OGF acts directly on the OGFr to inhibit cell proliferation [15,16]. The action is reversible, non-apoptotic, and independent of the immune system, other than inhibiting inflammatory T cells following immunization [27][28][29]. Based on in vitro and in vivo studies using human cancer cell lines and nude mice, OGF or LDN can be combined effectively with standard chemotherapeutic agents for an additive or enhanced repression of tumor progression [23].…”