Search

Properties of interferon productivity of several inducers of interferon, analogs of amixin, have been studied in vivo. It has been shown, that under the influence of injected agents the content of endogenic interferon in the blood serum of laboratory animals increased and their non-fractionated cells of the peripheral blood (splenocites and macrophages) synthesized alpha- and gamma-interferon.

Candida albicans is an increasingly important opportunistic fungal pathogen in immunocompromised patients. Natural killer (NK) cells constitute an important immune effector mechanism and are involved in the response to different pathological disorders. We wished to determine if this immune mechanism is involved in the specific response to C. albicans. Tilorone hydrochloride and related compounds have been described to display antiviral and antitumoral activity, as well as to enhance NK cell activity. In this study, we show the antimicrobial activity of different tilorone analogues and the enhanced resistance of tilorone-treated mice in experimental systemic candidiasis. We also present data suggesting that there is a correlation between NK cell activation and the resistance to experimental systemic candidiasis. Thus, it seems that the immunosurveillance of metastatic spread and the infection by C. albicans share some immune effector mechanisms, in particular activation of NK cells.

Tolerance and interferon-inducing activity of amixine, an interferon inducer, was studied by the double-blind method clinically in healthy volunteers given tableted amixine orally in doses of 0.125-0.25 g by different schedules. According to clinical laboratory examinations and studies of indirect parameters of labor capacity amixine was found to be tolerable for man. The amount of interferon in the blood serum depended on the schedule of administration of the inducer, the optimal being 1-2 amixine tablets at least 2 days apart.

A single administration of amixin followed by oral infection with mouse hepatitis virus provided protection of 40%-50% animals for 72 hours and normalized the interferon status. In parallel with decreasing level of virus-induced endogenous interferon the interferon-inhibiting activity of lymphocytes of the infected animals increased and approached normal levels.

The national preparation amixine induces interferon (IF) production in most of the people who have background values of serum IF. When the initial values of serum IF are high, after administration of amixine they decline to the background ones. A certain group of subjects (approximately 25%) is not sensitive to amixine. The IF content in the blood serum of such subjects does not change before or after administration of amixine. Its use should be limited to 4-5 administrations weekly, because its longer use leads to the exhaustion of the IF system in people.

Tilorone aza-analogues, derivatives of 4,7-phenanthroline and 1,8-diazafluorene, were examined as DNA-complexing agents by spectral and electrophoretic methods. The binding process includes at least two types of interactions: electrostatic and, possibly, intercalation. Complex formation with the denatured DNA was also observed, but its nature remained unsolved. Binding and thermodynamic parameters were determined. All ligands studied showed weak antiviral activity and essentially no interferon induction when assayed in vitro and in vivo. It was concluded that interferon induction by tilorone may involve specific cell receptors or intermediaries.

Among low molecular interferon inducers preparations were selected which were capable of inducing interferon (IFN) synthesis after oral administration and advantageous for further clinical use. The dynamics of interferon production was studied after oral administration of three national low molecular interferon inducers. The selected preparations: a synthetic inducer, amiksin, and 2 natural compounds (gossypol derivatives), kagocel-1 and PXL-6, stimulated high levels of interferon production (from 10,000 to 20,000 IU/ml) in the intestinal tract of the animals 4 hours after induction and protected the animals from hepatitis virus of mice (the Meshcherin strain) after oral administration 24 hours before infection (35-55%). Amiksin and PXL-6 produced significant protection (p less than 0.01 or 0.001)--40 or 50%, respectively, when administered 4 hours before virus infection.