In vivo and in vitro stimulation of mouse spleen leukocytes by BL-20803, a low-molecular-weight interferon inducer

Abstract

BL-20803, a low-molecular-weight compound, although able to elicit circulating interferon in the mouse, failed to protect cultured cell lines in vitro from infection by interferon-sensitive viruses. Of the tissues analyzed for interferon content after oral administration of the drug to mice, spleen and lung contained the largest amounts of the virus inhibitor. Spleen cells from such dosed animals when isolated into in vitro cultures elaborated small amounts of interferon into the culture medium. The time sequence of acquisition by spleen cells of the ability to produce interferon closely correlated with the kinetics of development of the circulating interferon response in the intact mouse. When spleen cells were separated on the basis of adherence or nonadherence to a plastic surface, the bulk of the interferon activity was found to be associated with the adherent cells. Upon exposure to BL-20803 in cell culture, adherent cells and, to a lesser extent, nonadherent cells from untreated mice were stimulated to produce interferon-like activity. The biological behavior of BL-20803 is shown to have striking similarities with that of the structurally different low-molecular-weight inducer tilorone hydrochloride.

Interferon induction by radioprotective mercaptoalkylamines and derived thiophosphates

“…3. Mice DISCUSSION Most low-molecular-weight inducers of interferon unrelated to mercaptoalkylamines probably stimulate specialized cell types within the body, since they induce interferon formation in the whole animal but usually do not stimulate nonlymphoid cells in cultures (12,19,20). The current studies demonstrate that the aminothiols are different in that they stimulate both mouse and human cultures, as do high-molecular-weight polynucleotides and viruses (10).…”

“…Because of their possible use as radioprotective drugs, the pharmacology and toxicology of mercaptoalkylamines and thiophosphate derivatives have been studied in animals and man, and some have been shown to be relatively safe. A property of low-molecular-weight interferon inducers such as tilorone (12), BL-20803 (19), and MA-56 (20) is that they may be taken orally and still induce systemic interferon. Such a study is indicated for aminothiols.…”