Capsicum ethanol extracts and capsaicin enhance interleukin-2 and interferon-gamma production in cultured murine Peyer's patch cells ex vivo

• Published in: Life sciences (1973) 2007-04, Vol.80 (17), p.1553-1563
• Main Authors: Takano, Fumihide, Yamaguchi, Masaya, Takada, Satoko, Shoda, Satoko, Yahagi, Nobuo, Takahashi, Tomoya, Ohta, Tomihisa
• Format: Article
• Language: English
• Subjects: Administration, Oral; Analgesics, Non-Narcotic - pharmacology; Animals; Capsaicin; Capsaicin - analogs & derivatives; Capsaicin - pharmacology; Capsicum; Capsicum - chemistry; Cell Proliferation - drug effects; Cells, Cultured; Concanavalin A - pharmacology; Cytokines; Dose-Response Relationship, Drug; Drug Antagonism; Drug Combinations; Ethanol - chemistry; Interferon-gamma - metabolism; Interleukin-2 - metabolism; Male; Mice; Mice, Inbred C57BL; Peyer's patch; Peyer's Patches - cytology; Peyer's Patches - drug effects; Peyer's Patches - metabolism; Plant Extracts - pharmacology; T-Lymphocyte Subsets - cytology; T-Lymphocyte Subsets - drug effects; Th1/Th2; TRPV Cation Channels - antagonists & inhibitors; TRPV Cation Channels - metabolism; TRPV1
• ISSN: 0024-3205; 1879-0631
• DOI: 10.1016/j.lfs.2007.01.031

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 μg/ml) and capsaicin (3 and 30 μM) resulted in suppression of interleukin (IL)-2, interferon (IFN)-γ, 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-γ 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-γ 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-γ 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-γ +) 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.