ABSTRACT
In experiments on two model systems L929/VSV and RF/ HSV-1 in vitro we have studied the antiviral activity of new structural analogues of tilorone--4,4'-bis[2-(diethyl-amino)ethoxy]diphenyl dihydrochloride and 2-methoxy-carbonyl-4-4'-bis[2-(diethylamino)ethoxy]diphenyl dihydrochloride. In experiments the tested substances were administered in preventive and therapeutic schemes. The preventive scheme confirms the existence of a correlation between IFN production under the influence of tested substances and their antiviral activity. It is shown that diphenyls are able to inhibit the development of viral cytopathic effect induced by DNA- and RNA-containing viruses. Diphenyl derivatives are less toxic than tilorone and could be considered as promising substances for further research to develop new antiviral drugs.
Subject(s)
Antiviral Agents/pharmacology , Biphenyl Compounds/pharmacology , Fibroblasts/drug effects , Herpesvirus 1, Human/drug effects , Vesiculovirus/drug effects , Animals , Cell Line , Cytopathogenic Effect, Viral/drug effects , Fibroblasts/virology , Herpes Simplex/drug therapy , Herpes Simplex/virology , Herpesvirus 1, Human/physiology , Humans , Inhibitory Concentration 50 , Maximum Tolerated Dose , Mice , Models, Biological , Rats , Tilorone/pharmacology , Vesicular Stomatitis/drug therapy , Vesicular Stomatitis/virology , Vesiculovirus/physiologyABSTRACT
Several ovarian disorders in women are associated with autoimmune factors. In this study it was investigated a level of cytokines--TNF-alpha and IFNs in ovarian homogenate and blood serum at ovarian autoimmune damage of mammals. Experimental immune ovarian failure was induced in CBA mice by either immunization with allogenic ovarian extracts or administration of xenogenic anti-ovarian antibodies. Both models were accompanied with abnormalities in production of immunoregulatory cytokines. These data confirm the importance of definition of proinflammatory cytokine level for disclosing immune mechanisms which lay in a pathogenesis autoimmune ovarian diseases of female reproductive organs.
Subject(s)
Autoimmune Diseases , Cytokines/blood , Ovarian Diseases/immunology , Animals , Autoimmune Diseases/blood , Disease Models, Animal , Female , Interferons/blood , Mice , Mice, Inbred CBA , Ovarian Diseases/blood , Ovary/immunology , Tumor Necrosis Factor-alpha/bloodABSTRACT
Human cord blood cells were shown to produce interferon-alpha- and -gamma in vitro, both spontaneously and following adequate induction. Transplantation of human blood cord cells to mice led to endogenous interferonogenesis activation, serum interferon levels as well as interferon-alpha and interferon-gamma synthesis by activated peripheral blood leucocytes becoming higher. The maximal interferon accumulation in murine blood sera following transplantation did not coincide with interferonogenesis dynamics observed due to the effect of standard early and late interferon inducers - poly I:C and ridostin, respectively. Interferonogenesis activation was accompanied by increased functional activty of phagocytic system cells.
