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Interaction of immunomodulant substances in mouse experiments with special regard to drug sensitivity and bacterial
P Anderlik1, I Szeri, K Antmann
1Institute of Microbiology, Semmelweis University Medical School, Budapest, Hungary.
Abstract:
In acute toxicity experiments changes in drug sensitivity and in the rate of bacterial translocation (BT) were investigated in mice treated with immunomodulatory drugs: dianhydrogalactitol (DAG) in doses 20 and 30 mg/kg, chlorpromazine (CPZ) in doses 60 and 75 mg/kg and Mannozym (M) in dose equivalent to 40 mg per kg zymosan. The drugs were used separately or in combination. The sensitivity of mice to immunosuppressive DAG or CPZ was higher in the case of combined treatment than that of separately treated ones. The rate of BT was also higher in mice receiving combined treatment. Pretreatment with M exerting an immunostimulatory effect, influenced neither the sensitivity of mice to DAG or CPZ nor the very low normal rate of BT. The present results reinforced the authors' earlier observations that the effects of immunosuppressive drugs cumulated in and caused more serious damage of the organism. The increase in drug sensitivity to immunosuppressive agents may be connected with an increased rate of BT and effect of endotoxin.
Insights
Combined immunosuppressive drugs (dianhydrogalactitol and chlorpromazine) increased mouse sensitivity and bacterial translocation (BT). Immunostimulatory Mannozym had no effect. This suggests cumulative damage from combined immunosuppressants.
Area of Science:
- Immunopharmacology
- Toxicology
- Microbiology
Background:
- Immunomodulatory drugs can alter host defense mechanisms.
- Bacterial translocation (BT) is a marker of gut barrier integrity.
- Understanding drug interactions is crucial for managing toxicity.
Purpose of the Study:
- To investigate the effects of combined immunomodulatory drugs on drug sensitivity and bacterial translocation (BT) in mice.
- To evaluate the impact of dianhydrogalactitol (DAG), chlorpromazine (CPZ), and Mannozym (M) on acute toxicity.
Main Methods:
- Acute toxicity experiments were conducted in mice.
- Mice were treated with DAG, CPZ, or Mannozym, alone or in combination.
- Drug sensitivity and the rate of bacterial translocation (BT) were measured.
Main Results:
- Combined treatment with immunosuppressive DAG or CPZ significantly increased mouse sensitivity compared to separate treatments.
- The rate of bacterial translocation (BT) was also elevated in mice receiving combined immunosuppressive drugs.
- Immunostimulatory Mannozym did not affect drug sensitivity or BT rates.
Conclusions:
- The cumulative effects of immunosuppressive drugs can lead to more severe organismal damage.
- Increased drug sensitivity to immunosuppressive agents may be linked to elevated BT and endotoxin effects.
- Immunostimulatory agents like Mannozym may not mitigate the risks associated with combined immunosuppressants.