Calcium channel blocker prevents T helper type 2 cell-mediated airway inflammation.
BACKGROUND
Ca(2+) signaling controls the production of T helper (Th) type 2 cytokines known to be deleterious in asthma. Recently, we showed that Ca(2+) signaling was dihydropyridine (DHP)-sensitive in Th2 lymphocytes and that the DHP derivate, nicardipine, used in the treatment of cardiovascular pathologies, prevents Th2-dependent B cell polyclonal activation.


OBJECTIVE
We tested the effect of nicardipine in experimental allergic asthma.


METHODS
BALB/c mice immunized with ovalbumin (OVA) in alum and challenged with intranasal OVA were treated with nicardipine once the Th2 response, or even airway inflammation, was induced. We also tested the effect of nicardipine in asthma induced by transferring OVA-specific Th2 cells in BALB/c mice exposed to intranasal OVA. We checked the impact of nicardipine on T-cell responses and airway inflammation.


RESULTS
Nicardipine inhibited in vitro Ca(2+) response in Th2 cells. In vivo, it impeded the development of Th2-mediated airway inflammation and reduced the capacity of lymphocytes from lung-draining lymph nodes to secrete Th2, but not Th1, cytokines. Nicardipine did not affect antigen presentation to CD4(+) T lymphocytes, nor the initial localization of Th2 cells into the lungs of mice exposed to intranasal OVA; however, it reduced the production of type 2 cytokines and the amplification of the Th2 response in mice with asthma. Conversely, nicardipine had no effect on Th1-mediated airway inflammation.


CONCLUSIONS
Nicardipine improves experimental asthma by impairing Th2-dependent inflammation. This study could provide a rationale for developing drugs selectively targeting DHP receptors of Th2 lymphocytes, potentially beneficial in the treatment of asthma.
Gomes
Bruno
B
INSERM, U563, CHU Purpan, Place du Dr Baylac, 31024 Toulouse Cedex 3, France.
Cabral
Marilena Djata
MD
Gallard
Alexandra
A
Savignac
Magali
M
Paulet
Pierre
P
Druet
Philippe
P
Mariamé
Bernard
B
Moreau
Marc
M
Leclerc
Catherine
C
Guéry
Jean-Charles
JC
Pelletier
Lucette
L
D000281:Administration, Intranasal; D000818:Animals; D001249:Asthma / Q000139:chemically induced / Q000276:immunology / Q000517:prevention & control*; D001992:Bronchoalveolar Lavage Fluid / Q000166:cytology; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology / Q000473:pathology; D002118:Calcium / Q000378:metabolism; D002121:Calcium Channel Blockers / Q000627:therapeutic use*; D049109:Cell Proliferation / Q000187:drug effects; D003713:Dendritic Cells / Q000276:immunology / Q000378:metabolism / Q000473:pathology; D004195:Disease Models, Animal; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D007249:Inflammation / Q000276:immunology* / Q000473:pathology / Q000517:prevention & control; D007274:Injections, Intraperitoneal; D007424:Intracellular Fluid / Q000378:metabolism; D008168:Lung / Q000276:immunology / Q000378:metabolism / Q000473:pathology; D008213:Lymphocyte Activation / Q000187:drug effects / Q000276:immunology; D051379:Mice; D008807:Mice, Inbred BALB C; D008822:Mice, Transgenic; D009529:Nicardipine / Q000627:therapeutic use*; D010047:Ovalbumin / Q000008:administration & dosage / Q000633:toxicity; D012720:Severity of Illness Index; D018418:Th2 Cells / Q000276:immunology* / Q000473:pathology
D002121:Calcium Channel Blockers; D010047:Ovalbumin; D009529:Nicardipine; D002118:Calcium