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Effects of calcium channel blockers on in vivo cellular immunity in mice
1Department of Medicine, University of Maryland Hospital, Baltimore 21201.
Abstract:
In vitro studies have shown that calcium channel blockers (CCB) inhibit lectin-induced lymphocyte proliferation. However, no in vivo effects have been documented yet. In this study we evaluated the effects of CCB on in vivo cellular immunity by using contact sensitivity to oxazolone in mice. From 15 to 30 twelve-week-old female C3H mice were randomized into: 0.9 NS (sham), ethanol, CsA, dexamethasone (DXM), verapamil, diltiazem, and nifedipine groups. These study agents were given daily from day 1 to day 9 subcutaneously to the shaved abdominal wall. The mice were sensitized with oxazolone to the abdominal wall on day 2 and challenged with oxazolone on the right ear on day 8. Delayed-type hypersensitivity was measured on day 10 and defined as the difference in thickness between the right (challenged) and left (control) ear of each mouse. The mean DTH of each study group was compared with that of the sham, and the statistical significance was determined by a Student's t test. The percentage of change in DTH from the sham was also calculated as: (mean DTH of study drug group-mean DTH of sham group)/mean DTH of sham group x 100%. A negative value meant a suppressive effect on DTH; a positive value, an enhancing one. The CsA, DXM, and nifedipine all had significant suppressive effects on DTH. Verapamil had a significant enhancing effect. Ethanol and diltiazem had no significant effect. More studies employing other antigens with several other cell-mediated response measurements along with DTH quantification should be done in order to determine the specificity of the immunosuppressive effect of CCB as well as the potential of any calcium antagonist as an adjuvant suppressive agent.
Insights
Calcium channel blockers (CCB) were tested for in vivo immune effects. Nifedipine suppressed cellular immunity, while verapamil enhanced it, suggesting CCBs may modulate immune responses.
Area of Science:
- Immunology
- Pharmacology
Background:
- In vitro studies indicate calcium channel blockers (CCB) inhibit lectin-induced lymphocyte proliferation.
- However, in vivo data on CCB effects on cellular immunity remain limited.
Purpose of the Study:
- To investigate the in vivo effects of CCB on cellular immunity using a mouse model.
- To evaluate the impact of specific CCBs on delayed-type hypersensitivity (DTH).
Main Methods:
- Female C3H mice were treated with CCBs (verapamil, diltiazem, nifedipine), cyclosporine A, dexamethasone, or controls.
- Contact sensitivity to oxazolone was induced and measured as ear thickness difference (DTH).
Main Results:
- Nifedipine, cyclosporine A, and dexamethasone significantly suppressed DTH.
- Verapamil demonstrated a significant enhancing effect on DTH.
- Ethanol and diltiazem showed no significant impact on DTH.
Conclusions:
- Nifedipine exhibits immunosuppressive properties in vivo, contrasting with verapamil's immune-enhancing effects.
- Further research is needed to elucidate the specific mechanisms and potential of CCBs as immunomodulatory agents.