Objective: To determine if aqueous, polysaccharide-containing Echinacea purpurea extracts taken orally increase pro-inflammatory cytokine responses ex vivo.
Design: In two separate studies, the levels of TNF-alpha (TNF), interleukins 2 and 6 (IL-2 and IL-6) and interferon gamma (IFN-γ) secreted by phytohemagglutinin (PHA)-stimulated peripheral blood mononuclear cells (PBMC) from healthy adults randomized to take one of three E. purpurea formulations or placebo orally for 10 consecutive days were measured. Blood was obtained from participants at baseline and on days 2, 3, 7, and 10 while on study medication. PBMC were isolated and stimulated with PHA for 24 h, and supernatants collected for measurement of pro-inflammatory cytokine levels.
Outcome Measures: Primary outcomes were peak concentrations of PHA-induced TNF, IL-2, IL-6, and IFN-γ from PBMC isolates collected while on study medication. Cytokine responses of PBMC from participants randomized to one of the Echinacea formulations were compared with those of placebo recipients by regression analysis.
Results: Cytokine levels were obtained from mitogen-activated PBMC from 86 participants, collected while on study medication. No significant differences in the peak levels of PBMC-secreted TNF, IL-2, IL-6 and IFN-γ were observed between PBMC from those taking active Echinacea preparation vs. a placebo. After adjusting for age, a trend toward increased IL-6 secreted by PHA-stimulated PBMC isolated on day 3 of oral administration was observed for the group taking one of the E. purpurea formulations compared with placebo (P=0.064).
Conclusions: Oral administration of E. purpurea did not significantly enhance peak pro-inflammatory cytokine responses in mitogen-stimulated PBMC.
Barrett BP, Brown RL, Locken K, Maberry R, Bobula JA, D’Alessio D. Treatment of the common cold with unrefined echinacea. A randomized, double-blind, placebo-controlled trial. Ann Intern Med. 2002; 137(12):939–946.
Taylor JA, Weber W, Standish L, et al. Efficacy and safety of echinacea in treating upper respiratory tract infections in children: a randomized controlled trial. J Am Med Assoc. 2003; 290(21):2824–2830.
Weber W, Taylor JA, Stoep AV, Weiss NS, Standish LJ, Calabrese C. Echinacea purpurea for prevention of upper respiratory tract infections in children. J Altern Complement Med. 2005; 11(6):1021–1026.
Turner RB, Bauer R, Woelkart K, Hulsey TC, Gangemi JD. An evaluation of Echinacea angustifolia in experimental rhinovirus infections. N Engl J Med. 2005; 353(4):341–348.
Schoop R, Klein P, Suter A, Johnston SL. Echinacea in the prevention of induced rhinovirus colds: a meta-analysis. Clin Ther. 2006; 28(2):174–183.
Shah SA, Sander S, White CM, Rinaldi M, Coleman CI. Evaluation of echinacea for the prevention and treatment of the common cold: a meta-analysis. Lancet Infect Dis. 2007; 7(7):473–480.
O’Neil J, Hughes S, Lourie A, Zweifler J. Effects of echinacea on the frequency of upper respiratory tract symptoms: a randomized, double-blind, placebo-controlled trial. Ann Allergy Asthma Immunol. 2008; 100(4):384–388.
Barrett B, Brown R, Rakel D, et al. Echinacea for treating the common cold: a randomized trial. Ann Intern Med. 2010; 153(12):769–777.
Karsch-Völk M, Barrett B, Kiefer D, Bauer R, Ardjomand-Woelkart K, Linde K. Echinacea for preventing and treating the common cold. Cochrane Database Syst Rev. 2014(2):CD000530.
Foster B, Drouin C, Krantis A, et al. Chemical marker profile and biological effects of natural products containing Echinacea. J Complement Integ Med. 2005; 2(1), doi: 10.2202/1553-3840.1026 .
Bauer R. Chemistry, analysis and immunological investigations of Echinacea phytopharmaceuticals. In: Wagner H, ed. Immunomodulatory Agents from Plants. Basel: Birkhauser Verlag; 1999. pp. 41–88.
Charrois TL, Hrudey J, Vohra S. Echinacea. Pediatr Rev. 2006; 27(10):385–387.
Wagner H, Stuppner H, Schafer W, Zek M. Immunologically active polysaccharides of Echinacea purpurea cell cultures. Phytochemistry. 1988; 27:119–126.
Goel V, Chang C, Slama JV, et al. Alkylamides of Echinacea purpurea stimulate alveolar macrophage function in normal rats. Int Immunopharmacol. 2002; 2(2–3):381–387.
Sasagawa M, Cech NB, Gray DE, Elmer GW, Wenner CA. Echinacea alkylamides inhibit interleukin-2 production by Jurkat T cells. Int Immunopharmacol. 2006; 6(7):1214–1221.
Woelkart K, Marth E, Suter A, et al. Bioavailability and pharmacokinetics of Echinacea purpurea preparations and their interaction with the immune system. Int J Clin Pharmacol Ther. 2006; 44(9):401–408.
Vohra S, Adams D, Hudson JB, et al. Selection of natural health products for clinical trials: a preclinical template. Can J Physiol Pharmacol. 2009; 87(5):371–378.
Wagner H, Breu W, Willer F, Wierer M, Remiger P, Schwenker G. In vitro inhibition of arachidonate metabolism by some alkamides and prenylated phenols. Planta Med. 1989; 55(6):566–567.
Cech NB, Tutor K, Doty BA, et al. Liver enzyme-mediated oxidation of Echinacea purpurea alkylamides: production of novel metabolites and changes in immunomodulatory activity. Planta Med. 2006; 72(15):1372–1377.
Burger RA, Torres AR, Warren RP, Caldwell VD, Hughes BG. Echinacea-induced cytokine production by human macrophages. Int J Immunopharmacol. 1997; 19(7):371–379.
Luettig B, Steinmuller C, Gifford GE, Wagner H, Lohmann-Matthes ML. Macrophage activation by the polysaccharide arabinogalactan isolated from plant cell cultures of Echinacea purpurea. J Natl Cancer Inst. 1989; 81(9):669–675.
Sullivan AM, Laba JG, Moore JA, Lee TD. Echinacea-induced macrophage activation. Immunopharmacol Immunotoxicol. 2008; 30(3):553–574.
Roesler J, Emmendorffer A, Steinmuller C, Luettig B, Wagner H, Lohmann-Matthes ML. Application of purified polysaccharides from cell cultures of the plant Echinacea purpurea to test subjects mediates activation of the phagocyte system. Int J Immunopharmacol. 1991; 13(7):931–941.
Kohlmeier JE, Woodland DL. Immunity to respiratory viruses. Annu Rev Immunol. 2009; 27:61–82.
Mullins RJ, Heddle R. Adverse reactions associated with echinacea: the Australian experience. Ann Allergy Asthma Immunol. 2002; 88(1):42–51.
Kalachnick J. Assessment sheet for monitoring of side-effects system. In: Poling A, Gadow K, Cleary J eds. Drug Therapy for Behavior Disorders: An Introduction. New York, NY: Pergamom Press; 1986. pp.153–155.
Morgan E, Varro R, Sepulveda H, et al. Cytometric bead array: a multiplexed assay platform with applications in various areas of biology. Clin Immunol. 2004; 110(3):252–266.
Chowdhury F, Williams A, Johnson P. Validation and comparison of two multiplex technologies, Luminex and Mesoscale Discovery, for human cytokine profiling. J Immunol Methods. 2009; 340(1):55–64.
Dupont NC, Wang K, Wadhwa PD, Culhane JF, Nelson EL. Validation and comparison of luminex multiplex cytokine analysis kits with ELISA: determinations of a panel of nine cytokines in clinical sample culture supernatants. J Reprod Immunol. 2005; 66(2):175–191.
Abbas A, Lichtman A, Pober J. Cytokines. In: Cellular and Molecular Immunology, 3rd ed. Philadelphia: WB Saunders; 1997. pp. 249–277.
Sharma M, Arnason JT, Burt A, Hudson JB. Echinacea extracts modulate the pattern of chemokine and cytokine secretion in rhinovirus-infected and uninfected epithelial cells. Phytother Res. 2006; 20(2):147–152.
Rininger JA, Kickner S, Chigurupati P, McLean A, Franck Z. Immunopharmacological activity of Echinacea preparations following simulated digestion on murine macrophages and human peripheral blood mononuclear cells. J Leukoc Biol. 2000; 68(4):503–10.
Goel V, Chang C, Slama J, et al. Echinacea stimulates macrophage function in the lung and spleen of normal rats. J Nutr Biochem. 2002; 13(8):487–492.
Tamta H, Pugh ND, Balachandran P, Moraes R, Sumiyanto J, Pasco DS. Variability in in vitro macrophage activation by commercially diverse bulk echinacea plant material is predominantly due to bacterial lipoproteins and lipopolysaccharides. J Agric Food Chem. 2008; 56(22):10552–10556.
Pugh ND, Tamta H, Balachandran P, et al. The majority of in vitro macrophage activation exhibited by extracts of some immune enhancing botanicals is due to bacterial lipoproteins and lipopolysaccharides. Int Immunopharmacol. 2008; 8(7):1023–1032.
Bussey RO, 3rd, Kaur A, Todd DA, et al. Comparison of the chemistry and diversity of endophytes isolated from wild-harvested and greenhouse-cultivated yerba mansa. Phytochem Lett. 2015; 11:202–208.
Raja HA, Kaur A, El-Elimat T, et al. Phylogenetic and chemical diversity of fungal endophytes isolated from (L) Gaertn. (milk thistle). Mycology. 2015; 6(1):8–27.
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