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Th1/Th2 balance: the hypothesis, its limitations, and implications for health and disease. Kidd P. Altern Med Rev. 2003 Aug;8(3):223-46. Review. PMID: 12946237 Th1 pathways typically produce activation of cytotoxic T lymphocytes (Tc), NK cells, macrophages, and monocytes, all of which can attack cancer cells and generally defend against tumors. 55 IFN-gamma and other Th1 cytokines are typically lower in advanced cancer patients, while the Th2 marker IL-4 can be higher or unchanged.56 Nodules of non-small cell lung cancer freshly removed from patients expressed a marked imbalance toward Th2, as did biopsy samples from basal cell carcinoma.57 In prostate cancer patients IL-2 was low (Th1) and IL-10 high.58 IL-10 is a confirmed Th1-suppressive cytokine, and heightened IL-10 is a common factor in cancer.55 IL-10 has a variety of suppressive effects that include inhibiting Th1 cytokine production, down-regulating APC and NK cell function, and lowering overall T-cell proliferation.57 Especially under the influence of IL-4 (Th2), tumor cells apparently up-regulate IL-10 that suppresses nearby killer cells. Tumor-derived IL-10 has been documented in lymphoma, ovarian carcinoma, melanoma, neuroblastoma, and renal cell and colon carcinoma.57 IL-12 is another cytokine that can be up-regulated by Th1 activity and inhibited by Th2.59 A low IL-12/IL-10 ratio was found in cervical cancer patients.55 Recent clinical studies suggest elevated IL-10 is predictive of a poor prognosis. 57 With both IL-4 and IL-10 being proven inhibitors of Th1 and promoters of Th2 activity, the recognized capability of cancerous tissue to suppress immunity is readily rationalized.

Combination immunotherapy of squamous cell carcinoma of the head and neck: a phase 2 trial. Barrera JL, Verastegui E, Meneses A, Zinser J, de la Garza J, Hadden JW. Arch Otolaryngol Head Neck Surg. 2000 Mar;126(3):345-51. PMID: 10722007 The natural cytokine mixture is a collection of natural human cytokines induced from human peripheral blood mononuclear cells. It contains IL-1, IL-2, IL-6, IL-8, IL-10, IL-12, interferon gamma, tumor necrosis factor , and granulocyte-macrophage and granulocyte colony-stimulating factor in nanogram quantities. It lacks IL-3, IL-4, IL-5, and IL-7. [...] This IRX-2 strategy uses perilymphatic local administration along with contrasuppression with low-dose cyclophosphamide and indomethacin and with zinc replacement therapy (as an immunorestorative). The data presented herein demonstrate that H&N SCC can respond very well to immunotherapy: there was a response rate of 100% in this series of 15 patients, with clinical reduction in tumor (1 complete response, 7 partial responses, and 7 minor responses) and histological evidence of tumor regression of 42%. Overall, the average combined estimated tumor reduction exceeded 70%. Also, patients with oral cancer noted marked analgesic and hemostatic effects from this therapy, with healing of oral lesions. [...] It is important to note that adjuvant chemotherapy is not used at INCAN. Many studies23 indicate that treatment with fluorouracil and cisplatin, the combination most in use, is effective for reducing tumors in the majority of patients; however, with no meaningful impact on survival, their routine use in the United States has recently been questioned.24-25 The expense, toxic effects, and lack of effectiveness of both drugs has made their use in other less affluent countries unwarranted. The current data on the use of IRX-2 in this and other protocols8-10 hint at improved survival, and a phase 3 randomized controlled study comparing this protocol with chemotherapy arm is to be initiat

A recently published study in Nutrition and Cancer (60(5), 643-651) by researchers at Kansai Medical University in Osaka, Japan has shown that AHCC (Active Hexose Correlated Compound) enhances immune function by increasing the number of dendritic cells (DCs). DCs are a key part of the immune system responsible for presenting foreign substances to other immune system cells. The study was conducted in a double-blind randomized fashion where twenty-one healthy subjects received a placebo or AHCC at 3.0 g/day for 4 weeks. Blood samples were obtained and measured at baseline and at 4 weeks. The number of circulating types of DCs was measured which included CD 11c+ DCs (myeloid DC population; DC1) and CD11c- DCs (lymphoid DC population; DC2). Other parameters measured included mixed-leukocyte reaction (MLR), natural killer (NK) cell activity, the proliferative response of T lymphocytes toward mitogen (phytohemagglutinin [PHA]) and cytokine production of interleukin (IL)-2, IL-4, IL-6, IL-10, interferon gamma-gamma, and (alpha)-tumor necrosis factor.

Conjugated linoleic acid promotes human adipocyte insulin resistance through NFkappaB-dependent cytokine production. Chung S, Brown JM, Provo JN, Hopkins R, McIntosh MK. J Biol Chem. 2005 Nov 18;280(46):38445-56. Epub 2005 Sep 9. PMID: 16155293 doi: 10.1074/jbc.M508159200 Collectively, these data demonstrate for the first time that trans-10, cis-12 CLA promotes NFkappaB activation and subsequent induction of IL-6, which are at least in part responsible for trans-10, cis-12 CLA-mediated suppression of peroxisome proliferator-activated receptor gamma target gene expression and insulin sensitivity in mature human adipocytes. In summary, our in vitro data demonstrate that a physiological level of trans-10, cis-12 CLA activates NFκB- and ERK1/2-dependent cytokine production, which together suppress PPARγ and Glut4 levels and lead to impaired glucose uptake. Studies are currently under way examining 1) how CLA regulates PPARγ and the expression of its target genes, 2) the specific signaling role of SV cells and adipocytes in mediating the TG-lowering actions of CLA, and 3) the CLA-induced, upstream signal that activates NFκB and ERK1/2.

Immunologic effects of national cholesterol education panel step-2 diets with and without fish-derived N-3 fatty acid enrichment. Meydani SN, Lichtenstein AH, Cornwall S, Meydani M, Goldin BR, Rasmussen H, Dinarello CA, Schaefer EJ. J Clin Invest. 1993 Jul;92(1):105-13. PMID: 8325975 doi:10.1172/JCI116537 the low-fat, high-fish diet significantly decreased the percentage of helper T cells whereas the percentage of suppressor T cells increased

March 7, 2005 Boston, MA - The anti-inflammatory effect of fish oils appears to be due to a powerful anti-inflammatory compound called resolvin (resolution-phase interaction product) E1, which is produced from eicosapentaenoic acid (EPA), Dr Makoto Arita (Brigham and Women's Hospital and Harvard Medical School, Boston, MA) and colleagues report in the March 7, 2005 issue of the Journal of Experimental Medicine [1]. Arita writes, "At nanomolar levels, resolvin E1 dramatically reduced dermal inflammation, peritonitis, dendritic cell migration, and interleukin (IL)-12 production.

Active Hexose Correlated Compound (AHCC) is an alpha-glucan rich nutritional supplement produced from the mycelia of shiitake (Lentinula edodes) of the basidiomycete family of mushrooms, and should not be confused or used as a drug or medicine.[1][2] AHCC was originally designed to lower high-blood pressure. However, researchers at Tokyo University found AHCC's influence upon the innate immune system highly beneficial and published the results in 1992, though not in the commonly indexed scientific literature. In this study, researchers found that AHCC significantly increased natural killer (NK) cell activity in cancer patients, and also enhanced the effects of killer T-cells, and cytokines (interferon, IL-12, TNF-alpha

These results suggest that combination chemotherapy (FO+Cur or Lim) may favorably modulate CD4+ T-cell-mediated inflammation.D ietary curcumin and limonin suppress CD4+ T-cell proliferation and interleukin-2 production in mice. Kim W, Fan YY, Smith R, Patil B, Jayaprakasha GK, McMurray DN, Chapkin RS. J Nutr. 2009 May;139(5):1042-8. Epub 2009 Mar 25. PMID: 19321585 doi:10.3945/jn.108.102772

Anti-inflammatory actions of lipoxin A4 and aspirin-triggered lipoxin are SOCS-2 dependent. Machado FS, Johndrow JE, Esper L, Dias A, Bafica A, Serhan CN, Aliberti J. Nat Med. 2006 Mar;12(3):330-4. Epub 2006 Jan 15. PMID: 16415877 doi:10.1038/nm1355\n

Modulation of inflammatory cytokines by omega-3 fatty acids. Kang JX, Weylandt KH. Subcell Biochem. 2008;49:133-43. Review. PMID: 18751910

Different effects of n-6 and n-3 polyunsaturated fatty acids on the activation of rat smooth muscle cells by interleukin-1 beta. Bousserouel S, Brouillet A, Béréziat G, Raymondjean M, Andréani M. J Lipid Res. 2003 Mar;44(3):601-11. Epub 2003 Jan 1. PMID: 12562859 doi:10.1194/jlr.M200092-JLR200

Stereochemical assignment, antiinflammatory properties, and receptor for the omega-3 lipid mediator resolvin E1. Arita M, Bianchini F, Aliberti J, Sher A, Chiang N, Hong S, Yang R, Petasis NA, Serhan CN. J Exp Med. 2005 Mar 7;201(5):713-22. PMID: 15753205 oi:10.1084/jem.20042031

Impact of fish oil enriched total parenteral nutrition on DNA synthesis, cytokine release and receptor expression by lymphocytes in the postoperative period. Schauder P, Röhn U, Schäfer G, Korff G, Schenk HD. Br J Nutr. 2002 Jan;87 Suppl 1:S103-10. PMID: 11895146 doi:10.1079/BJN2001463