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Published on: December 27, 2016
Diltiazem modulates monokine production in human mixed lymphocyte culture
A D'Ambrosio1, E Giacomini, B Camponeschi
1Immunology Department, Istituto Superiore di Sanità, Roma, Italy.
Insights
Calcium channel blockers like diltiazem impact immune responses. This study shows diltiazem modulates monokine production, specifically enhancing interleukin-1beta and reducing interleukin-6 in mixed lymphocyte cultures.
Area of Science:
- Immunology
- Pharmacology
- Transplantation Medicine
Background:
- Calcium channel blockers (CCBs) are utilized in transplantation for their known immunosuppressive properties.
- The impact of CCBs on cytokine production, particularly monokines, remains largely uninvestigated.
Purpose of the Study:
- To investigate the effect of the calcium antagonist diltiazem on cytokine production in human mixed lymphocyte cultures (MLCs).
- To explore the potential immunomodulatory effects of CCBs beyond their established immunosuppression.
Main Methods:
- Human mixed lymphocyte cultures (MLCs) were established from healthy donors.
- Cytokine production was quantified using enzyme-linked immunosorbent assay (ELISA), enzyme-linked immunospot (ELISPOT) assay, and reverse transcription polymerase chain reaction (RT-PCR).
Main Results:
- Diltiazem demonstrated a notable enhancement of interleukin-1beta (IL-1β) production in MLCs.
- A slight reduction in interleukin-6 (IL-6) levels was observed with diltiazem treatment.
- Tumor necrosis factor-alpha (TNF-α) levels were unaffected by diltiazem.
Conclusions:
- This study provides the first evidence of diltiazem modulating monokine production.
- These findings suggest that calcium antagonists may influence the function of monocytes and other antigen-presenting cells.
Background:
Calcium channel blockers are widely used in transplantation. Their immunosuppressive activity is well known and has been demonstrated both in vitro and in vivo. Nevertheless, their effect on cytokine production has never been reported.
Methods:
One-way mixed lymphocyte cultures (MLCs) have been obtained from healthy human subjects. Cytokine production has been assessed by three different methods: by enzyme-linked immunosorbent assay on supernatants of MLC, by enzyme-linked immunospot method on MLC cells for measuring cytokine-producing cells, and by the reverse transcription polymerase chain reaction technique on MLC cells for measuring cytokine mRNAs.
Results:
An interesting effect on proinflammatory monokines was observed: in this study, we demonstrate that the calcium antagonist diltiazem enhances interleukin-1beta and slightly reduces interleukin-6 production in MLC, but it has no effect on tumor necrosis factor-alpha levels.
Conclusion:
For the first time, a modulation of monokine production by diltiazem can be demonstrated. This evidence suggests that calcium antagonist drugs may exert effects on monocytes and possibly on other antigen-presenting cells.
