PRODUCTION OF IL-18 IN PRESENCE OF METAL-γ-GLOBULIN COMPLEXES

Present  study  used  in  vitro  cultures  of  human  peripheral  blood  cells  (PBC) with  addition  of γ-globulins, or  their complexes with copper and zinc, or  single copper and zinc  ions. We have  shown  that, among  common  pool  of  induced  cytokines,  interleukin-18  (IL-18)  was detectable  at  a concentration  of 24.4±1.03 to 33.25±0.90 pg/ml. IL-18 production in PBC after 24h treatment with γ-globulin-zinc complexes zinc was higher by 13-19%  than  following 24-h  incubation with control proteins, or zinc  ions. Accordingly,   IL-18 production in PBC after 72-h  incubation with γ-globulin copper  complexes  was higher than with control proteins.  In parallel  to  IL-18, human  PBC  produce detectable   interferon  (IFN, up  to  32 U/ml).  We have  shown  a  strong positive correlation between  the peaks of IFN  increase,  and elevated IL-18  levels  caused  by γ-globulin-metal  complexes.  Hence,  an opportunity  for  regulation of intracellular IL-18  and  IFN  production  by  γ-globulin-metal  complexes  at  the  level  of  basal  cell  functions  was  demonstrated  in  context  of  IFNγ induction, thus causing Th1-directed shift of immune response

INDUCTION OF IL-8 PRODUCTION BY THE METAL COMPLEXES OF γ-GLOBULIN FORMED WITH ZINC IONS

Abstract. This study has shown detectable production of IL-8, as a fraction of cytokine pool induced in culture of human peripheral blood cells (PBCs). Mean amounts of IL8 produced in presence of γ-globulin fraction proteins and/or their metal complexes with zinc ions varied from 575.0±27.77 to 6355.0±480.98 pg/ ml. The complexes of γ-globulin with zinc (48 h of culture) caused increase of IL-8 production that was 1.8-fold higher than with control γ-globulin and 1.4-fold higher than with of zinc ions alone (p < 0.02). Dynamic tracking of the cytokine levels has shown that PBCs induced with γ-globulin/metal complexes produced IL8 as a factor of prolonged or late-type response

Production of the Growth Factors GM-CSF, G-CSF, and VEGF by Human Peripheral Blood Cells Induced with Metal Complexes of Human Serum γ-Globulin Formed with Copper or Zinc Ions

As it was established in our previous studies, the proteins of human serum γ-globulin fraction could interact with copper or zinc ions distributed in the periglobular space, form metal complexes, and become able to perform effector functions differing due to the conformational shifts from those mediated by them in native conformation of their Fc regions. In the present work we have evaluated ability of the γ-globulin metal complexes formed with copper or zinc ions in the conditions like to the physiological ones to induce production or to regulate induction in the culture of freshly isolated human peripheral blood cells (PBC) of granulocyte (G) and granulocyte-macrophage (GM) colony-stimulating factors (CSF) as well as of vascular endothelial growth factor (VEGF). The γ-globulin metal complexes formed with both copper and zinc ions were found to similarly reduce production of GM-CSF, G-CSF, and VEGF induced in normal human PBC cultures by the control γ-globulins or by copper and zinc ions used alone. In context of theory and practice of inflammation the properties of the γ-globulin metal complexes might impact the basic knowledge in search of novel approaches to anti-inflammatory drugs development