Capsicum ethanol extracts and capsaicin enhance interleukin-2 and interferon-gamma production in cultured murine Peyer's patch cells ex vivo.
We investigated the effects of red pepper (Capsicum annuum Lin.) extracts (capsicum extract) and its main pungent capsaicin on T helper 1 (Th1) and 2 (Th2) cytokine production in cultured murine Peyer's patch (PP) cells in vitro and ex vivo. Direct administration of capsicum extract (1 and 10 mug/ml) and capsaicin (3 and 30 muM) resulted in suppression of interleukin (IL)-2, interferon (IFN)-gamma, IL-4 and IL-5 production. In an ex vivo experiment using PP cells removed from the mice after oral administration of capsicum extract (10 mg/kg/day for 4 consecutive days), IL-2, IFN-gamma and IL-5 increased in response to concanavalin A (Con A). Oral administration of 3 mg/kg/day capsaicin, one active constituent of the extract, also enhanced IL-2, INF-gamma and IL-4 production in response to Con A stimulation but did not influence the production of IL-5. Orally administered capsazepine (3 mg/kg/day), a selective transient receptor potential vanilloid 1 (TRPV1) antagonist, slightly enhanced IL-2 production also irrespective of Con A stimulation. The capsaicin-induced enhancement of both IL-2 and IFN-gamma production was not reduced by oral administration of capsazepine (3 mg/kg/day), suggesting a TRPV1 receptor-independent mechanism. Flow cytometric analysis revealed that the population of CD3(+) cells in the PP cells was significantly reduced while CD19(+) cells increased after oral administration of capsicum extract (1 and 10 mg/kg/day) and capsaicin (0.3 and 3 mg/kg/day). Capsazepine (3 mg/kg/day) weakly but significantly reversed these effects. Orally administered capsicum extract and capsaicin did not change the T cell subset (CD4(+) and CD8(+)), Th1 (IFN-gamma(+)) and T2 (IL-4(+)) ratio. These findings indicate that capsicum extract and capsaicin modulate T cell-immune responses, and their immunomodulatory effects on murine PP cells are partly due to both TRPV1-dependent and -independent pathway.
Takano
Fumihide
F
Department of Pharmacognosy and Chemistry of Natural Products, Faculty of Pharmaceutical Sciences, Kanazawa University, Kakuma-machi, Kanazawa 920-1192, Japan. takano@p.kanazawa-u.ac.jp
Yamaguchi
Masaya
M
Takada
Satoko
S
Shoda
Satoko
S
Yahagi
Nobuo
N
Takahashi
Tomoya
T
Ohta
Tomihisa
T
D000284:Administration, Oral; D018712:Analgesics, Non-Narcotic / Q000494:pharmacology*; D000818:Animals; D002211:Capsaicin / Q000031:analogs & derivatives / Q000494:pharmacology*; D002212:Capsicum / Q000737:chemistry*; D049109:Cell Proliferation / Q000187:drug effects; D002478:Cells, Cultured; D003208:Concanavalin A / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D004336:Drug Antagonism; D004338:Drug Combinations; D000431:Ethanol / Q000737:chemistry; D007371:Interferon-gamma / Q000378:metabolism*; D007376:Interleukin-2 / Q000378:metabolism*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D010581:Peyer's Patches / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D010936:Plant Extracts / Q000494:pharmacology*; D016176:T-Lymphocyte Subsets / Q000166:cytology / Q000187:drug effects; D050916:TRPV Cation Channels / Q000037:antagonists & inhibitors / Q000378:metabolism
D018712:Analgesics, Non-Narcotic; D004338:Drug Combinations; D007376:Interleukin-2; D010936:Plant Extracts; D050916:TRPV Cation Channels; C493921:TRPV1 protein, mouse; D003208:Concanavalin A; D000431:Ethanol; D007371:Interferon-gamma; C071423:capsazepine; D002211:Capsaicin