This subproject is one of many research subprojects utilizing theresources provided by a Center grant funded by NIH/NCRR. The subproject andinvestigator (PI) may have received primary funding from another NIH source,and thus could be represented in other CRISP entries. The institution listed isfor the Center, which is not necessarily the institution for the investigator.Red peppers (Capsicum frutescens) have been used for several thousand years as food additives and for a broad variety of medical applications in Indian, Native American, African and Chinese medical traditions. CP is the pungent component of red peppers. Chemically, it is a derivative of vanillyl amide, 8-methyl-N-vanillyl-6-noneamide and has a molecular weight of 305.42. The receptor for CP is vanilloid receptor 1 (VR1). VR1 has been shown to be highly expressed in nociceptive neurons of dorsal root and trigeminal ganglia. CP binds to VR1 on sensory neurons to convey the sensation of pain. Apart from its neurological functions CP has also been shown to be active immunologically, in generating more antibody-producing cells compared to untreated controls. Dietary CP in BALB/c mice has been shown to enhance lymphocyte proliferation and serum immunoglobulin levels. Inhalation of CPhas been shown to interfere with neural responses involved in inflammation in the lungs of Lewis rats and such interference modulates immunity to inhaled antigens. We and others have observed that mouse and human dendritic cells (DCs), a key cell type in immune responses, have the receptor for CP, and engagement of this receptor has powerful immune consequences. Our recent data suggest that intra-lesional administration of CP into a preexisting murine tumor results in retarded progression of the injected tumor regardless of whether the tumor is at its early or late stage. Further, it leads to significant inhibition of growth of other, un-injected tumors in the same animal. We have shown that only tumor cells but not normal cells undergo apoptosis in response to CP but CP elicited anti-tumor immunity is T cell mediated and tumor-specific.CP has been used previously in clinical studies. Intradermal and topical application of CP has been used to study mechanisms of allodynia and hyperalgesia and the efficacy of drugs in relieving the symptoms. The dose of CP variedfrom 20 to 250 n gg. Pain intensity and vital signs were monitored after CP administration. We have used intra lesional CP in mouse tumor model with MTD at a dose of 200 gg. The common toxicity noticed was scar at the injection site. Based upon our observations in the laboratory, we have hypothesized intra lesional use of CP in patients with melanoma may have immunological relevance in this disease.

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