ORIGINAL ARTICLE Immunomodulating Properties of Carrageenan from Tichocarpus crinitus Eduardas Cicinskas, 1,5 Aleksandra A. Kalitnik , 1,2 Yuriy A. Karetin , 1,2 Manoj Saravana Guru Mohan Ram, 1,3 Anant Achary, 3 and Anna O. Kravchenko 4 Abstract— Several in vivo immunotropic effects of κ/β-carrageenan isolated from the red algae Tichocarpus crinitus were studied, by orally administering it at 100 mg/kg/day to mice for 7 days. Serum levels of IFN-γ, IL-12, IL-1β, and IL-4 were measured. Carrageenan’ s ability to influence development of LPS-induced inflammation was also assessed. Oral administration of κ/β-carrageenan increased serum levels of all the studied cytokines at least twice in comparison to the intact mice, while intraperitoneal LPS injection at 1 mg/kg increased concentration of only the pro-inflammatory cytokines: IFN-γ, IL-12, and IL-1β. Furthermore, κ/β-carrageenan demonstrated a higher efficacy at inducing IFN-γ production than LPS. Previous 7-day-long oral carrageenan administration impaired development of LPS-induced inflammation: level of IL-1β dropped below that found in intact mice, while IFN-γ and IL-12 concentrations were at least 40% lower than in mice with LPS-induced inflammation. Murine peritoneal macrophages were also affected by the oral administration of the κ/β-carrageenan: their motility was increased, and morphology altered. In sum, we have demonstrated that κ/β-carrageenan, when administered orally, is not only not immuno- logically inert, but at the dose of 100 mg/kg possesses pharmacologically exploitable effects. KEY WORDS: κ/β-carrageenan; Tichocarpus crinitus; cytokines; immune cells; in vivo. BACKGROUND Carrageenans are a family of naturally occurring water-soluble linear sulfated galactans, composing cell wall of numerous species of red algae. Carrageenans con- sist of regularly alternating β-1,3- and α-1,4-linked D- galactosyl residues (G- and D-units), which are classified in accordance with the basic structure of disaccharide repeating unit (carrabiose), presence of 3,6-anhydrogalactose (DA-unit) as 4-linked residue, and numbers of sulfate groups per one disaccharide unit [1]. Thus, the most industrially exploited types of carrageenans – κ-, ι- and λ-carrageenans, 1 School of Biomedicine, School of Natural Sciences Far Eastern Federal University, 8 Sukhanova Street, Vladivostok, 690950, Russia 2 A. V. Zhirmunsky National Scientific Center of Marine Biology, Far Eastern Branch Russian Academy of Science, 17 Palchevskogo street, Vladivostok, 690022, Russia 3 Center for Research, Department of Biotechnology, Kamaraj College of Engineering and Technology, S.P.G.C. Nagar, K. Vellakulam, Madu- rai, 625701, India 4 G. B. Elyakov Pacific Institute of Bioorganic Chemistry, FEB RAS, 100- let Vladivostoku Prospect, Vladivostok, 690022, Russia 5 To whom correspondence should be addressed at School of Biomedicine, School of Natural Sciences Far Eastern Federal University, 8 Sukhanova Street, Vladivostok, 690950, Russia. E-mail: cicinskas@gmail.com 0360-3997/20/0000-0001/0 # 2020 Springer Science+Business Media, LLC, part of Springer Nature Inflammation ( # 2020) DOI: 10.1007/s10753-020-01216-x