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Mechanism of cellular suppression induced by oral tilorone treatment of mice
Abstract:
Specific-pathogen-free B6D2 F1 hybrid mice were treated orally with tilorone hydrochloride (100 mg/kg of body weight per day) and infected with sublethal doses of Listeria monocytogenes, Salmonella enteritidis, Mycobacterium bovis (BCG Pasteur), or M. tuberculosis Erdman. Daily tilorone treatment inhibited the cell-mediated response to all of the intracellular parasites, and most of the mice succumbed to the challenge. Tilorone suppressed delayed hypersensitivity responses to the microbial sensitins as well as to sheep erythrocytes. However, humoral responses (immediate hypersensitivity reactions) were stimulated. The types of growth curves obtained in the tilorone-treated mice were quite different from those observed in T-cell-depleted mice and tended to resemble those seen in sublethally irradiated (400 rads) animals. Leukocyte counts were depressed 10-fold by daily tilorone treatment. Both monocyte and granulocyte (but not large-lymphocyte) counts were depressed. There was an initial drop in small-lymphocyte counts with a later recovery phase. Tilorone treatment reduced the granulomatous response within the Salmonella-infected liver, suggesting that the drug interferes with the mobilization of the mononuclear defenses within the normal host.
Insights
Tilorone hydrochloride treatment impaired cell-mediated immunity in mice, increasing susceptibility to intracellular pathogens like Listeria and Salmonella. This immunosuppression affected leukocyte counts and granuloma formation, highlighting tilorone
Area of Science:
- Immunology
- Pharmacology
- Microbiology
Background:
- Tilorone hydrochloride is an immunomodulatory agent.
- Intracellular pathogens pose significant health challenges.
- Understanding drug effects on host defense is crucial.
Purpose of the Study:
- To investigate the impact of tilorone hydrochloride on cell-mediated immunity against intracellular bacterial infections.
- To assess the effects of tilorone on humoral immunity and leukocyte profiles.
Main Methods:
- Specific-pathogen-free mice were treated with tilorone hydrochloride.
- Mice were infected with Listeria monocytogenes, Salmonella enteritidis, Mycobacterium bovis, or Mycobacterium tuberculosis.
- Cell-mediated and humoral immune responses, leukocyte counts, and granulomatous responses were evaluated.
Main Results:
- Tilorone treatment inhibited cell-mediated immunity, leading to increased mortality in infected mice.
- Delayed hypersensitivity responses were suppressed, while humoral responses were enhanced.
- Leukocyte counts, particularly monocytes and granulocytes, were significantly depressed.
- Tilorone reduced granulomatous responses in Salmonella-infected livers.
Conclusions:
- Tilorone hydrochloride exhibits immunosuppressive properties, particularly against cell-mediated immunity.
- The drug alters immune cell populations and impairs host defense mechanisms against intracellular pathogens.
- Tilorone's effects on immune responses warrant further investigation for therapeutic implications.