Protection against Klebsiella pneumoniae using lithium chloride in an intragastric infection model
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Nina Tsao1, Chih-Feng Kuo2, Ching-Chen Chiu3
1Department of Biological Science and Technology, I-Shou University, Kaohsiung City, Taiwan ninatsao@isu.edu.tw.
Abstract:
Intragastric Klebsiella pneumoniae infections of mice can cause liver abscesses, necrosis of liver tissues, and bacteremia. Lithium chloride, a widely prescribed drug for bipolar mood disorder, has been reported to possess anti-inflammatory properties. Using an intragastric infection model, the effects of LiCl on K. pneumoniae infections were examined. Providing mice with drinking water containing LiCl immediately after infection protected them from K. pneumoniae-induced death and liver injuries, such as necrosis of liver tissues, as well as increasing blood levels of aspartate aminotransferase and alanine aminotransferase, in a dose-dependent manner. LiCl administered as late as 24 h postinfection still provided protection. Monitoring of the LiCl concentrations in the sera of K. pneumoniae-infected mice showed that approximately 0.33 mM LiCl was the most effective dose for protecting mice against infections, which is lower than the clinically toxic dose of LiCl. Surveys of bacterial counts and cytokine expression levels in LiCl-treated mice revealed that both were effectively inhibited in blood and liver tissues. Using in vitro assays, we found that LiCl (5 μM to 1 mM) did not directly interfere with the growth of K. pneumoniae but made K. pneumoniae cells lose the mucoid phenotype and become more susceptible to macrophage killing. Furthermore, low doses of LiCl also partially enhanced the bactericidal activity of macrophages. Taken together, these data suggest that LiCl is an alternative therapeutic agent for K. pneumoniae-induced liver infections.
Insights
Lithium chloride (LiCl) treatment protected mice from Klebsiella pneumoniae liver infections. LiCl reduced bacterial counts and improved survival by enhancing macrophage activity, suggesting its potential as an alternative therapy.
Area of Science:
- Infectious Diseases
- Pharmacology
- Immunology
Background:
- Klebsiella pneumoniae intragastric infections in mice lead to severe liver damage, including abscesses, necrosis, and bacteremia.
- Lithium chloride (LiCl), a medication for bipolar disorder, exhibits anti-inflammatory properties.
- The therapeutic potential of LiCl against K. pneumoniae infections remains largely unexplored.
Purpose of the Study:
- To investigate the efficacy of lithium chloride (LiCl) as a therapeutic agent against Klebsiella pneumoniae-induced liver infections in a murine model.
- To determine the optimal dosage and timing of LiCl administration for protective effects.
- To elucidate the underlying mechanisms by which LiCl confers protection against K. pneumoniae infection.
Main Methods:
- Establishment of an intragastric K. pneumoniae infection model in mice.
- Administration of varying doses of LiCl via drinking water at different time points post-infection.
- Assessment of survival rates, liver injury markers (AST, ALT), bacterial loads, cytokine levels, and macrophage phagocytic activity.
- In vitro assays to evaluate LiCl's direct effect on K. pneumoniae growth and its impact on macrophage bactericidal activity.
Main Results:
- LiCl administration significantly improved survival and reduced liver necrosis in a dose-dependent manner.
- Optimal protection was observed with approximately 0.33 mM LiCl, a sub-toxic concentration.
- LiCl treatment inhibited bacterial counts and cytokine expression in blood and liver tissues, enhanced macrophage killing of K. pneumoniae, and partially boosted macrophage bactericidal activity without directly affecting bacterial growth.
Conclusions:
- Lithium chloride demonstrates significant therapeutic potential in mitigating K. pneumoniae-induced liver infections in mice.
- LiCl's protective effects are mediated through enhanced host immune responses, particularly macrophage-mediated killing, rather than direct antimicrobial action.
- LiCl represents a promising alternative therapeutic strategy for treating K. pneumoniae liver infections at clinically achievable, non-toxic doses.
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