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Cutaneous leishmaniasis in mice: resistance to glucan immunotherapy, either alone or combined with chemotherapy
Abstract:
Leishmania braziliensis, L. mexicana, and L. garnhami were studied for their ability to produce American cutaneous leishmaniasis, using C57BL/6 female mice as the animal model. No significant difference in the clinical course of mouse foot pad infection was found between the three American Leishmania species studied. In general, the incubation period varied from 2-4 weeks. Mice developed only local swelling and sometimes ulceration at the sites of inoculation. After 4 weeks of progress lesions began to decrease without obvious impact on the general health of the mice. When glucan immunotherapy (120 - 240 mg/kg body weight) was initiated previous to, or simultaneously with, infection the development of foot pad lesions was not significantly inhibited, this despite clear evidence of generalized stimulation of the reticuloendothelial system. On the other hand, pentavalent antimony at high doses (1,000 - 1,500 mg/kg) induced only a significant lengthening of the latent period. However, different combinations of glucan and pentavalent antimony (various doses of each drug, timing of administration, or changes in the sequence of use of both drugs) did not significantly alter the clinical course of American Leishmania infection as compared with pentavalent antimony alone. Thus, not only were glucan or glucantime alone unable to cure the infection (as evidenced by some animals which showed rapidly growing lesions some time after the end of treatment), but no potentiation was observed.
Insights
This study found that glucan immunotherapy and pentavalent antimony alone or in combination did not significantly improve American cutaneous leishmaniasis in mice. Treatment failed to inhibit lesion development or cure the infection effectively.
Area of Science:
- Parasitology
- Immunology
- Infectious Diseases
Background:
- American cutaneous leishmaniasis is a significant health concern.
- Understanding the efficacy of immunotherapies and antimonials is crucial for treatment development.
Purpose of the Study:
- To evaluate the efficacy of glucan immunotherapy and pentavalent antimony, alone and in combination, against American cutaneous leishmaniasis in a mouse model.
- To assess the impact of these treatments on lesion development and disease progression.
Main Methods:
- Infection of C57BL/6 female mice with Leishmania braziliensis, L. mexicana, and L. garnhami.
- Administration of glucan immunotherapy and/or pentavalent antimony at various doses and timings.
- Clinical monitoring of foot pad lesions and general health of infected mice.
Main Results:
- No significant difference in clinical course was observed between the three Leishmania species.
- Glucan immunotherapy did not inhibit lesion development, despite immune stimulation.
- Pentavalent antimony alone only prolonged the incubation period.
- Combinations of glucan and pentavalent antimony showed no significant improvement over pentavalent antimony alone.
- Neither treatment alone nor in combination effectively cured the infection.
Conclusions:
- Glucan immunotherapy and pentavalent antimony exhibit limited efficacy in treating American cutaneous leishmaniasis in this mouse model.
- Combined therapy does not offer significant advantages over monotherapy with pentavalent antimony.
- Further research is needed to develop more effective treatment strategies for leishmaniasis.