Lactobacillus casei ssp.casei Induced Th1 Cytokine Profile and Natural Killer Cells Activity in Invasive Ductal Carcinoma Bearing Mice


Lactic acid bacteria which are  used  as  probiotics  have  ability to  modulate  immune responses and modify immune mechanisms. It has also been indicated that some strains of this family can affect the immune responses against solid tumors.
In the present work, we proposed to study the effects of oral administration of L.cacesi ssp casei on the NK cells cytotoxicity and also production of cytokines in spleen cells culture of BALB/c mice bearing invasive ductal carcinoma. 30 female In-bred  BALB/c mice, were used and divided in two groups of test and control each containing 15 mice. Every day from 2 weeks before tumor transplantation 0.5 ml of PBS containing 2.7×108 CFU/ml of L.casei spp  casei  was  orally administered  to  the  test  mice  and  it  was  followed  3  weeks after transplantation as well with 3 days interval between each week. Control mice received an equal volume of PBS in a same manner.
Results showed that oral administration of L. casei significantly increased the production of IL-12 and IFN-γ (P<0.05) and increased the natural killer cells (NK) cytotoxicity in spleen cells culture of test mice (P<0.05). It has also been demonstrated that the growth rate of tumor in the test mice was decreased and their survival was significantly prolonged in comparison to the controls.
Our findings suggest that daily intake of L.casei can improve immune responses in mice bearing invasive ductal carcinoma, but further studies are needed to investigate the other involving mechanisms in this case.

1. Stewart TH, Heppner GH. Immunological enhancement of breast cancer. Parasitology 1997; 115:141–153.
2. Marrogi AJ, Munshi A, Merogi AJ. Study of tumor infiltrating lymphocytes and transforming growth factor- beta as prognostic factors in breast carcinoma. Int J Cancer 1997; 74(5):492–501.
3. Disis ML, Park KH. Immunomodulation of breast cancer via tumor antigen specific Th1. Cancer Res Treat. 2009;41(3):117-21.
4. Papazahariadou M, Athanasiadis GI, Papadopoulos E, Symeonidou I, Hatzistilianou M, Castellani ML, et al. Involvement of NK cells against tumors and parasites. Int J Biol Markers 2007; 22(2):144-53.
5. Rizzello V, Bonaccorsi I, Dongarrà ML, Fink LN, Ferlazzo G. Role of natural killer and dendritic cell crosstalk in immunomodulation by commensal bacteria probiotics. J Biomed Biotechnol 2011; 473097.
6. De Roos NM, Katan MB. Effects of probiotic bacteria on diarrhea, lipid metabolism, and carcinogenesis: a review of papers published between 1988 and 1998. Am J Clin Nutr 2000; 71(2):405–11.
7. Hori T, Kiyoshima J, Yasui H. Effect of an oral administration of Lactobacillus casei strain Shirota on the natural killer activity of blood mononuclear cells in aged mice. Biosci Biotechnol Biochem 2003; 67(2):420–2.
8. Maassen C B, Van Holten-Neelen C, Balk F, Heijne den Bak-Glashouwer M, Leer RJ, Laman JD, et al. Strain- dependent induction of cytokine profiles in the gut by orally administered Lactobacillus strains. Vaccine 2000;18(23):2613–23.
9. Trinchieri G. Interleukin-12: a cytokine produced by antigenpresenting cells with immunoregulatory functions in the generation of T-helper cells type 1 and cytotoxic lymphocytes. Blood 1994; 84(12):4008–27.
10. Matsuzaki T, Yamazaki R, Hashimoto S, Yokokura T.The effect of oral feeding of Lactobacillus casei strain Shirota on immunoglobulin E production in mice. J Dairy Sci 1998; 81(1):48-53.
11. Attia M, Weiss DW. Immunology of spontaneous mammary carcinomas in mice. Acquired tumor resistance and enhancement in strain mice infected with mammary tumor virus. Cancer Res 1996; 26(8):1787-800.
12. Jin H, Li Y, Ma Z, Zhang F, Xie Q, Gu D, et al. Effect of chemical adjuvants on DNA vaccination. Vaccine 2004; 22(21-22):2925–35.
13. Mahdavi M, Ebtekar M, Azadmanesh K, Khorramkhorshid HR, Rahbarizadeh F, Yazdi MH, et al. HIV-1 Gag p24-Nef fusion peptide induces cellular and humoral immune response in a mouse model. Acta Virol 2010; 54:131–6.
14. Murosaki S, Muroyama K, Yamamato Y, Yoshikai Y.Antitumor effect of heat-killed Lactobacillus plantarum L-137 through restoration of impaired interleukin-12 production in tumor-bearing mice. Cancer Immunol Immunother 2000; 49(3):157-64.
15. Segawa S, Nakakita Y, Takata Y, Wakita Y, Kaneko T,Kaneda H, et al. Effect of oral administration of heat- killed Lactobacillus brevis SBC8803 on total and ovalbumin-specific immunoglobulin E production through the improvement of Th1/Th2 balance. Int J Food Microbiol 2008; 121(1):1–10.
16. Yazdi MH, Soltan Dallal MM, Hassan ZM, Holakuyee M, Agha Amiri S, Abolhassani M, et al. Oral administration of Lactobacillus acidophilus induces IL-12 production in spleen cell culture of BALB/c mice bearing transplanted breast tumor. Br J Nutr 2010; 104(2):227-32.
17. Subleski JJ, Wiltrout RH, Weiss JM. Application of tissue-specific NK and NKT cell activity for tumor immunotherapy. J Autoimmun 2009; 33(3-4):275-81.
18. Gill HS, Rutherfurd KJ, Cross ML. Dietary probiotic supplementation enhances natural killer cell activity in elderly: an investigation of age related immunological changes. J Clin Immunol 2001; 21(4):264-71.
19. Gill HS, Rutherfurd KJ, Cross ML, Gopal PK.Enhancement of immunity in the elderly by dietary supplementation with theprobiotic Bifidobacterium lactis HN019. Am J Clin Nutr 2001; 74(6):833-9.
20. Bunout D, Barrera G, Hirsch S, Gattas V, de la Maza MP, Haschke F, et al. Effects of nutritional supplementation on the immune response and cytokine production in free- living Chilean elderly. J Parent Ent Nutr 2004; 28(5):348-54.
21. Parra MD, Martinez de Morentin BE, Cobo JM, Mateos A, Martinez JA. Daily ingestion of fermented milk containing Lactobacillus casei DN14001 improves innate- deffense capacity in healthy middle-age people. J Physiol Biochem 2004; 60(2):85-91.
22. Schroder K, Hertzog PJ, Ravasi T, Hume DA.Interferon-gamma: an overview of signals, mechanisms and functions. J Leukoc Biol 2004; 75(2):163-89.
23. Fujiwara D, Inoue S, Wakabayashi H, Fujii T. The Anti- Allergic Effects of Lactic Acid Bacteria Are Strain Dependent and Mediated by Effects on both Th1/Th2 Cytokine Expression and Balance. Int Arch Allergy Immunol 2004; 135(3):205–15.
24. Sayers TJ, Mason LH, Wiltrout TA. Trafficking and activation of murine natural killer cells: differing roles for IFN-gamma and IL-2. Cell Immunol 1990; 127(2):311-26.
25. Segawa S, Nakakita Y, Takata Y, Wakita Y, Kaneko T, Kaneda H, et al. Effect of oral administration of heat- killed Lactobacillus brevis SBC8803 on total and ovalbumin-specific immunoglobulin Ep roduction through the improvement of Th1/Th2 balance. Int J Food Microbiol 2008; 121(1):1–10.
26. Kaplan DH, Shankaran V, Dighe AS, Stockert E, Aguet M, Old LJ, et al. Demonstration of an interferon gamma- dependent tumor surveillance system in immunocompetent mice. Proc Natl Acad Sci 1998;23(13):7556-61.

IssueVol 11, No 2 (2012) QRcode
Invasive ductal carcinoma Lactobacillus casei NK cytotoxicity Th1 cytokines

Rights and permissions
Creative Commons License This work is licensed under a Creative Commons Attribution-NonCommercial 4.0 International License.
How to Cite
Soltan Dallal MM, Yazdi MH, Holakuyee M, Mohammad Hassan Z, Abolhassani M, Mahdavi M. Lactobacillus casei ssp.casei Induced Th1 Cytokine Profile and Natural Killer Cells Activity in Invasive Ductal Carcinoma Bearing Mice. Iran J Allergy Asthma Immunol. 1;11(2):183-189.