Preliminary Report Echinacea alkylamides inhibit interleukin-2 production by Jurkat T cells Masa Sasagawa a , Nadja B. Cech b , Dean E. Gray c , Gary W. Elmer d , Cynthia A. Wenner a, ⁎ a Bastyr University, Department of Basic Sciences, School of Natural Health Sciences, Kenmore, WA 98028, United States b University of North Carolina Greensboro, Department of Chemistry and Biochemistry, P.O. Box 26170, Greensboro, NC 27405, United States c Midwest Research Institute, Kansas City, MO 64110, United States d University of Washington, Department of Medicinal Chemistry, Box 357610, Seattle, WA 98195, United States Received 22 November 2005; received in revised form 9 January 2006; accepted 6 February 2006 Abstract Alkylamides present in Echinacea species have reported immunomodulatory actions, yet their direct effects on T lymphocytes, key mediators of antiviral immunity, are poorly understood. We hypothesized that constituents present in ethanolic extracts of Echinacea species exert direct immunomodulatory effects on human Jurkat T cells. Modulation of IL-2 production by submaximally stimulated Jurkat cells was determined in response to treatment with extracts prepared from dried aerial parts of Echinacea purpurea. Cells were treated with the extracts, with alkylamides or caffeic acid derivatives isolated from Echinacea species, or with corresponding ethanol vehicle, in the absence or presence of phytohemagglutinin and phorbal ester. E. purpurea extracted in a solvent mixture of 95:5 ethanol/water dose-dependently inhibited IL-2 production. This IL-2 inhibitory activity correlated with the presence of alkylamides but not caffeic acid derivatives, as determined by high performance liquid chromatography/electrospray ionization-mass spectrometry analysis. Simultaneous measurement of secreted IL-2 by ELISA and cell viability by the XTT assay showed that the 95:5 ethanol/water extract of E. purpurea was both IL-2 suppressive and cytotoxic at 50 and 100 μg/mL. Lower concentrations from 6.25 to 25 μg/mL significantly decreased IL-2 production but not cell viability. Alkylamides at concentrations found in a 50 μg/mL extract decreased IL-2 production by approximately 50%. Two Echinacea-derived alkylamides significantly depressed IL-2 production but not cell viability in a dose-dependent manner. Thus, alkylamides present in E. purpurea suppress the ability of activated Jurkat T cells to produce IL-2 independently of direct, cytotoxic effects. © 2006 Elsevier B.V. All rights reserved. Keywords: Alkylamides; Echinacea; Interleukin-2 (IL-2); Jurkat T cells 1. Introduction Perennial plants in the genus Echinacea have been traditionally used by Native Americans to treat cold and flu symptoms, reduce inflammation and heal wounds [1]. One of the main constituent groups present in ethanol/ water extracts of Echinacea with reported bioactivity is International Immunopharmacology 6 (2006) 1214 – 1221 www.elsevier.com/locate/intimp ⁎ Corresponding author. Tel.: +1 425 602 3163; fax: +1 425 602 3079. E-mail address: cindyw@bastyr.edu (C.A. Wenner). 1567-5769/$ - see front matter © 2006 Elsevier B.V. All rights reserved. doi:10.1016/j.intimp.2006.02.003