Browse > Article
http://dx.doi.org/10.5352/JLS.2009.19.3.411

Effects of Chitosan on the Production of Th1 and Th2 Cytokines in Mice  

Kim, Kwang-Hyuk (Department of Microbiology, Institute for Medicine, Kosin University College of Medicine)
Publication Information
Journal of Life Science / v.19, no.3, 2009 , pp. 411-416 More about this Journal
Abstract
Chitosan is derived from chitin by a process of controlled deacetylation. In the present study, we investigated the effects of chitosan on the production of cytokines such as interleukin-2 (IL-2), interferon-$\gamma$ (IFN-$\gamma$), interleukin-4 (IL-4), and interleukin-10 (IL-10) in mice. The culture supernatants of splenocytes exposed with chitosan alone or chitosan plus cell stimulants, lipopolysaccharide (LPS), concanavalin A (Con A), and phytohemagglutinin-P (PHA-P) were harvested to assay IL-2, IFN-$\gamma$, IL-4, and IL-10 production. IL-2, IFN-$\gamma$, and IL-4 from splenocytes exposed to chitosan showed a greater increase compared to the PBS control group. IL-2 and IFN-$\gamma$ levels in the culture supernatants from splenocytes exposed to LPS+chitosan were higher than those of the groups exposed to LPS alone. IL-4 and IL-10 levels in the culture supernatants from splenocytes exposed to LPS+chitosan were lower than those of the groups exposed to LPS only. These findings demonstrate that chitosan upregulates the immune responses by Th1 cytokines (IL-2 and IFN-$\gamma$) and downregulates those by Th2 cytokines (IL-4 and IL-10) in LPS-associated immunity. These results show the potential of its usefulness for balancing the Th1/Th2 immune response, if more research results were accumulated.
Keywords
Chitosan; cytokine; IL-2; IFN-$\gamma$; IL-4; IL-10; mice;
Citations & Related Records
Times Cited By KSCI : 2  (Citation Analysis)
연도 인용수 순위
1 Westerink, M. A. J., S. L. Smithson, N. Srivastava, J. Blonder, C. Coeshott, and G. J. Rosenthal. 2002. ProJuvant (Pluronic F127 /chitosan) enhances the immune response to intranasally administered tetanus toxoid. Vaccine 20, 711-723   DOI   ScienceOn
2 Wu, K. Y., M. Wu, M. L. Fu, H. Li, Y. Yang, H. Zhang, C. Cheng, Z. Z. Wang, X. Y. Wang, X. B. Lu, D. G. Liu, H. Li, and R. Gao. 2006. A novel chitosan CpG nanoparticle regulates cellular and humoral immunity of mice. Biomed. Environ. Sci. 19, 87-95
3 Xie, Y., N. J. Zhou, S. Y. Xiong, J. Chen, Y. F. Gong, N. H. Lu, and C. W. Wang. 2007. Anti-helicobacter pylori effect and regulation of T helper response of chitosan. Zhonghua Nei Ke Za Zhi 46, 220-223
4 Xie, Y., N. J. Zhou, Y. F. Gong, X. J. Zhou, J. Chen, S. J. Hu, N. H. Lu, and X. H. Hou. 2007. Th immune response induced by H pylori vaccine with chitosan as adjuvant and its relation to immune protection. World J. Gastroenterol. 13, 1547-1553   DOI
5 Yermak, I. M., V. N. Davidova, V. I. Gorvach, P. A. Luk'yanov, T. F. Solov'eva, A. J. Buwitt-Beckman U, E. T. Rietschel, and Y. S. Ovodov. 2005. Forming and immunological properties of some lipopolysaccharide-chitosan complexes. Biochimie 88, 23-30   DOI   ScienceOn
6 Peluso, G., O. Petillo, M. Ranieri, M. Santin, L. Ambrosio, D. Calabro, B. Avallone, and G. Balsamo. 1994. Chitosanmediated stimulation of macrophage function. Biomaterials 15, 1215-1220   DOI   ScienceOn
7 Seferian, P. G. and M. L. Martinez. 2001. Immune stimulating activity of two new chitosan containing adjuvant formulations. Vaccine 19, 661-668   DOI   ScienceOn
8 Shikata, F., H. Tokumitsu, H. Ichikawa, and Y. Fukumori. 2002. In vitro cellular accumulation of gadolinium incorporated into chitosan nanoparticles designed for neutron-capture therapy of cancer. Eur. J. Pharm. Biopharm. 53, 57-63   DOI   ScienceOn
9 Ueno, H., T. Mori, and T. Fujinaga. 2001. Topical formulation and wound healing applications of chitosan. Adv. Drug Deliv. Rev. 52, 105-115   DOI   ScienceOn
10 Takashi, M., O. Masahiro, M. Mitsunobu, U. Keisuke, T. Seiichi, O. Yoshiharu, M. Sabro, and F. Toru. 1997. Effect of chitin and its derivatives on the proliferation and cytokine production of fibroblasts in vitro. Biomaterials 18, 947-951   DOI   ScienceOn
11 van der Lubben, I. M., G. Kersten, M. M. Fretz, C. Beuvery, J. C. Verhoef, and H. E. Junginger. 2002. Chitosan microparticles for mucosal vaccination against diphtheria: oral and nasal efficacy studies in mice. Article in press. Vaccine 3600, 1-9
12 van der Lubben, I. M., J. C. Verhoef, G. Borchard, and H. E. Junginger. 2001. Chitosan for mucosal vaccination. 2001. Adv. Drug Deliv. Rev. 52, 139-144   DOI   ScienceOn
13 Mire-Sluis, A. R. and R. Thorpe. 1998. CYTOKINES. pp. 19-400, Academic Press. San Diego, California
14 Pae, H. O., W. G. Seo, N. Y. Kim, G. S. Oh, G. E. Kim, Y. H. Kim, H. J. Kwak, Y. G. Yun, C. D. Jun, and H. T. Chung. 2001. Induction of granulocytic differentiation in acute promyelocytic leukemia cells (HL-60) by water-soluble chitosan oligomer. Leuk. Res. 25, 339-346   DOI   ScienceOn
15 Iqbal, M., W. Lin, I. Jabbal-Gill, S. S. Davis, M. W. Steward, and L. Illum. 2002. Nasal delivery of chitosan-DNA plasmid expressing epitopes of respiratory syncytial virus (RSV) induces protective CTL responses in BALB/c mice. Article in press. Vaccine 3585, 1-8
16 Kato, Y., H. Onishi, and Y. Machida. 2002. Efficacy of lactosaminated and intact N-succinyl-chitosan-mitomycin C conjugates against M5076 liver metastatic cancer. J. Pharm. Pharmacol. 54, 529-537   DOI   ScienceOn
17 Koide, S. S. 1998. Chitin-chitosan: properties, benefits, and risks. Nutrition Res. 18, 1091-1101   DOI   ScienceOn
18 Kato, Y., H. Onishi, and Y. Machida. 2001. Lactosaminated and intact N-succinyl-chitosans as drug carriers in liver metastasis. Int. J. Pharm. 226, 93-106   DOI   ScienceOn
19 Kimura, Y. and H. Okuda. 1999. Prevention by chitosan of myelotoxicity, gastrointestinal toxicity and immunocompetent organic toxicity induced by 5-fluorouracil without loss of antitumor activity in mice. Jpn. J. Cancer Res. 90, 765-774   DOI
20 Kimura, Y., N. Sawai, and H. Okuda. 2001. Antitumor activity and adverse reactions of combined treatment with chitosan and doxorubicin in tumor-bearing mice. J. Pharmacol. 53, 1373-1378   DOI   ScienceOn
21 Li, H., R. Gao, M. Wu, M. Fu, K. Wu, Y. Yang, X. Wang, Z. Wang, and S. Liu. 2004. Effects of entrapment of murine interleukin-2 gene with chitosan nanoparticles on expression of mIL-2 gene and on regulation of immune response in mice. Sheng Wu Yi Xue Gong Cheng Xue Za Zhi 21, 947-952
22 McNeela, E. A., D. O'Connor, I. Jabbal-Gill, L. Illum, S. S. Davis, M. Pizza, S. Peppoloni, R. Rappuoli, and K. H. Mills. 2000. A mucosal vaccine against diphtheria: formulation of cross reacting material (CRM(197)) of diphtheria toxin with chitosan enhances local and systemic antibody and Th2 responses following nasal delivery. Vaccine 19, 1188-1198   DOI   ScienceOn
23 Chung, Y. S., K. H. Kim, Y. K. Jeong, and M. W. Chang. 2004. Effects of chitosan on anti-tumor activity in mice. J. Life Sci. 14, 209-214   DOI   ScienceOn
24 Akbuga, J., S. Ozbas-Turan, and N. Erdogan. 2004. Plasmid- DNA loaded chitosan microspheres for in vitro IL-2 expression. Eur. J. Pharm. Biopharm. 58, 501-507   DOI   ScienceOn
25 Baek, K. S., E. K. Won, and S. Y. Choung. 2007. Effects of chitosan on serumcytokine levels in elderly subjects. Arch. Pharm. Res. 30, 1550-1507   DOI   ScienceOn
26 Chen, W. R., H. Liu, J. W. Ritchey, K. E. Bartels, M. D. Lucroy, and R. E. Nordquist. 2002. Effect of different components of laser immunotherapy in treatment of metastatic tumors in rats. Cancer Res. 62, 4295-4299
27 Eroglu, M., S. Irmak, A. Acar, and E. B. Denkbas. 2002. Design and evaluation of a mucoadhesive therapeutic agent delivery system for postoperative chemotherapy in superficial bladder cancer. Int. J. Pharm. 235, 51-59   DOI   ScienceOn
28 Howling, G. I., P. W. Dettmar, P. A. Goddard, F. C. Hampson, M. Dornish, and E. J. Wood. 2001. The effect of chitin and chitosan on the proliferation of human skin fibroblasts and keratinocytes in vitro. Biomaterials 22, 2959-2966   DOI   ScienceOn