Met-enkephalin is a pentapeptide present in different tissues. This neuropeptide exerts various modulatory signals on different cell types, which led to its application in clinical medicine (Plotnikoff et al., Clin Immunol Immunopathol, 82:93, 1997 ; Štambuk et al., Uveitis Today, Elsevier, Amserdam, pp 319-322, 1998). The authors review Met-enkephalin therapy in 38 patients with autoimmune diseases (uveitis, Behçet's disease, allergic conjunctivitis/rhinitis, optic neuritis, multiple sclerosis, SLE/overlap syndrome, rheumatoid arthritis, Evans syndrome/hemolytic anemia). No toxicity or side-effects were observed during the Met-enkephalin therapy ranging from 6 months to >3 years. Met-enkephalin (peptid-M, LUPEX) was administered s.c. dissolved in 2 ml of physiological saline, 0.2 - 0.3 mg/kg 5 times weekly for 4 weeks. Afterwards, the weekly dose was gradually reduced every 4 weeks till 5 mg weekly. Clinical parameters including EDSS, evoked potentials, visual field, MRI and ultrasonographic findings were observed and evaluated to obtain better insight into the efficacy of Met-enkephalin therapy. In addition to the beneficial clinical effects and significant reduction in the number and severity of relapses the peptide modulated serum IFN, IFN-gamma, phagocyte, NK and lymphocyte functions. During Met-enkephalin therapy relapses were rare, mild, and in most cases did not require additional corticosteroid therapy, i.e. only the rise of Met-enkephalin dose was sufficient. However, the synergistic action of Met-enkephalin and corticosteroids is discussed considering the fact that it is a part of ACTH precursor molecule (Blalock, Immunol Today 15:504, 1994). It is emphasised that in severe autoimmune diseases parallel administration of Met-enkephalin and corticosteroids enables significant reduction of the steroid dose (to e.g. 2-4 mg dexamethasone daily during relapse). Treatment protocols for combined immunotherapy of Met-enkephalin and corticosteroids or i.v. IgG (7S, 5S+7S) have also been defined (Štambuk et al., Int J Thymology 5:448, 1997). Finally, we re-evaluate classic opioid hypothesis of Met-enkephalin action considering Met-enkephalin interactions with its probable calpastatin receptor site, that was recently defined by means of the Molecular Recognition Theory (Štambuk et al., Croat Chem Acta 71:591, 1998). This sequence shares homology to the Rapamycin and FK506 receptor site (FKB3_HUMAN, aa 108-111), which may account for the immuno-suppressive effects of Met-enkephalin in vitro and in vivo independently of the opioid system and without mutagenetic effects.

Javno zdravstvo i zdravstvena zaštita,Temeljne medicinske znanosti,Kemija