γ-Globulin fraction proteins and their metal complexes with copper cations in induction of IL-8 production.

Plasma γ-globulin fraction proteins, copper cations, and metal complexes formed by copper cations with human serum γ-globulin induce the production of up to 4.0 ng/ml IL-8 by human blood cells. Protein modified by copper cations is 1.3-1.7-fold (p < 0.001-0.01) more potent than control γ-globulin and 1.3-fold (p < 0.001) more potent than copper cations alone. Analysis of the time course of IL-8 production demonstrated that IL-8 is produced as a prolonged or delayed response cytokine under conditions of this induction.

Induction of TNF-α production by metal complexes of γ-globulin fraction proteins and copper and zinc cations.

Plasma γ-globulin fraction proteins, copper and zinc cations, and metal complexes of these cations and human serum γ-globulin induce the production of TNF-α by human blood cells. The protein modified by zinc cations is by 1.4-1.7 times more potent (p<0.001-0.01) than control γ-globulin in inducing the production of TNF-α, while metal complex formed by γ-globulin and copper is by 1.9-2.2 times more potent that the control protein (p<0.001). Under conditions of experimental induction, TNF-α is produced as a typical early response cytokine. During long-term incubation, copper cations lose the ability to induce TNF-α production, while in combination with γ-globulin these cations produce a synergistic effect with the control protein.

Production of early IL-1ß induced by human serum γ-globulin metal complexes.

Plasma γ-globulin fraction proteins, copper and zinc cations, and metal complexes formed by them with human serum γ-globulin induce the production of early (24-h incubation) IL-1ß by human blood cells. The protein modified by Zn cations 1.2 times more actively (p<0.01) induced early IL-1ß than the control γ-globulin, while γ-globulin metal complex with copper was 1.4 times less active (p<0.1) than the control protein. The regularities of induction changed over the course of 48-h incubation: zinc cations chelated by γ-globulin fraction protein reduced, while copper cations stimulated the realization of the protein induction potential in the metal complex.

Production of late IFN-α induced by plasma γ-globulin fraction proteins and their metal complexes.

Plasma γ-globulin fraction proteins, copper and zinc cations, and metal complexes they form with human serum γ-globulin induce the production of IFN-α by human blood cells throughout the periods of up to 72 h. Zinc cation-modified protein by 1.6 times (p<0.05) more actively induces late IFN-α than the control γ-globulin; γ-globulin-copper metal complex is 2-fold (p<0.002) more effective than the control protein. The results indicate that functional relationships between the components inducing the production of late IFN-α differ from the effects realized during the early period of induction.

Detection of IFN-alpha produced in the presence of plasma gamma-globulin fraction proteins.

Interferon-alpha was detected in IFN pool produced by human leukocytes in the presence of gamma-globulin fraction proteins, copper and zinc cations, and metal-modified gamma-globulins. The cytokine appeared in culture medium at early terms (24 h) of incubation, is characterized by acid resistance, and is neutralized by antibodies to IFN-alpha. The content of IFN-alpha in supernatants of induced leukocytes reached 60-90 pg/ml and correlated with antiviral activity of the samples. Zinc bound to human serum gamma-globulin attenuated and copper stimulated the realization of IFN-inducing characteristics of the protein at early terms of incubation.