ABSTRACT
Type II interferon is known to be produced in mice infected with Trypanosoma cruzi. Therefore, interferon production was investigated in mice infected with Trypanosoma equiperdum. Interferon was found in the sera of mice infected with T. equiperdum from day 1 after infection until death on day 5. The maximal level of interferon appeared before parasitemia was detected, a finding showing that the endogenous interferon probably had no significant influence on the course of infection. Unexpectedly, the serum interferon was characterized as type I by its stability at pH 2 and by its neutralization by antiserum to virus-induced mouse interferon. The production of two different types of interferon in mice infected with T. cruzi and T. equiperdum may have been due to the dissimilar life cycles of the two trypanosomes in the white mouse.
Subject(s)
Interferon Inducers , Interferons/metabolism , Trypanosomiasis/parasitology , Animals , Cattle , Female , Hydrogen-Ion Concentration , Interferons/blood , Mice , Neutralization Tests , RabbitsABSTRACT
Attempts were made to stimulate interferon production in human cell cultures by two related acridin drugs, mepacrine and Acranil. Tilorone was included for comparison. In human embryo lung fibroblasts and in normal human leukocytes only tilorone stimulated some interferon production. All three drugs stimulated modest interferon production in two lymphoblastoid cell lines. All three drugs enhanced the Sendai virus-induced interferon production in lymphoblastoid cells.
Subject(s)
Acridines/pharmacology , Fluorenes/pharmacology , Interferon Inducers , Interferons/biosynthesis , Tilorone/pharmacology , Cells, Cultured , Fibroblasts/metabolism , Humans , Leukocytes/metabolism , Molecular Weight , Quinacrine/pharmacologyABSTRACT
The antiviral activity and induction of interferon-like substance by mepacrine (quinacrine, Atabrine) and Acranil in mice, described previuosly, was studied in more detail and compared with tilorone. The serum substance induced by Acranil was characterized as mouse interferon. Acranil, given parenterally, proved to be as strong as tilorone regarding interferon stimulation, in spite of the presence of only one side chain in the Acrainl molecule. Mepacrine was found to be a wealer interferon inducer than either tilorone or Acranil. The mode of interferon induction by Acranil and tilorone (effect of metabolic inhibitors, hyporesponsiveness to repeated doses, correlation between acute toxicity and antiviral activity, failure of effectiveness in chicks and chicken embryo tissue culture) was found comparable. However, the body temperature reactions of mice to the drugs were different: a striking hypothermic effect of tilorone, a lower one of mepacrine and the absence of body temperature depression by Acranil was observed.
Subject(s)
Acridines/pharmacology , Fluorenes/pharmacology , Interferon Inducers/pharmacology , Tilorone/pharmacology , Aminacrine/analogs & derivatives , Animals , Body Temperature/drug effects , Chick Embryo , Chickens , Culture Techniques , Cycloheximide/pharmacology , Dactinomycin/pharmacology , Female , Interferons/blood , Male , Mice , Propanolamines/pharmacology , Quinacrine/pharmacology , Rabbits , Vaccinia virus/drug effectsABSTRACT
Several drugs with certain structural similarities (tricyclic ring system with dialkylaminoalkyl side chains) to tilorone, a potent interferon inducer, were screened for antiviral activity in vivo. Two acridine drugs, Acranil and quinacrine, were found to be effective, the former being almost as protective as tilorone and the latter less so. Both agents induced an interferon-like substance which could be detected in the serum of treated mice. The concentration of the inhibitory factor in the serum was highest after exposure to tilorone, followed in turn by Acranil and quinacrine, based on the administration of equal weights of drugs. Both tilorone and Acranil induced lower levels of circulating interferon-like substance in Balb/c mice than in other strains of mice. The serum factor induced by Acranil was shown to be stable at pH 2.
