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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.

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.

Schleithoff SS, Zittermann A, Tenderich G, Berthold HK, Stehle P, Koerfer R. Vitamin D supplementation improves cytokine profiles in patients with congestive heart failure: a double-blind, randomized, placebo-controlled trial.Am J Clin Nutr. 2006 Apr;

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

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

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

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

Effects of probiotic bacteria and their genomic DNA on TH1/TH2-cytokine production by peripheral blood mononuclear cells (PBMCs) of healthy and allergic subjects. Ghadimi D, Fölster-Holst R, de Vrese M, Winkler P, Heller KJ, Schrezenmeir J. Immunobiology. 2008;213(8):677-92. Epub 2008 Apr 2. PMID: 18950596 doi:10.1016/j.imbio.2008.02.001

The effects of whole mushrooms during inflammation. Yu S, Weaver V, Martin K, Cantorna MT. BMC Immunol. 2009 Feb 20;10:12. PMID: 19232107 doi:10.1186/1471-2172-10-12 In RAW 264.7 cells the induction of TNF-α production was highest in LPS and WB stimulated rather than the crimini, maitake, oyster, or shitake stimulated cells. The differences might be a result of differences in the quantity of the immunomodulatory substance or substances and or differences in solubility of mushrooms in the DMSO used to produce the extracts. However, the direction of the changes (increase versus decrease) were not different among the mushroom treatments. The lack of differential effects on cytokine secretion by the mushroom extracts suggests that the whole mushrooms must share a common component(s) that act to regulate immune function.

Consuming cheese from ewe's milk, rich in conjugated linoleic acid (CLA), may reduce markers linked to heart disease, suggest results from a small Italian study. Researchers from the University of Florence report that ewe's milk rich in cis-9, trans-11 CLA produced favourable changes in inflammatory cytokines and platelet aggregation, both of which are associated with atherosclerosis, or hardening of the arteries due to the build-up of fatty deposits on artery walls.

Floyd Chilton and colleagues wanted to examine whether theses fatty acids might have other effects, and developed a dietary intervention strategy in which 27 healthy humans were fed a controlled diet mimicking the w6/w3 ratios of early humans over 5 weeks. They then looked at the gene levels of immune signals and cytokines (protein immune messengers), that impact autoimmunity and allergy in blood cells and found that many key signaling genes that promote inflammation were markedly reduced compared to a normal diet, including a signaling gene for a protein called PI3K, a critical early step in autoimmune and allergic inflammation responses. This study demonstrates, for the first time in humans, that large changes in gene expression are likely an important mechanism by which these omega fatty acids exert their potent clinical effects

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.

"Língzhī (traditional Chinese: 靈芝; simplified Chinese: 灵芝; Japanese: reishi; Korean: yeongji, hangul: 영지) is the name for one form of the mushroom Ganoderma lucidum, and its close relative Ganoderma tsugae. Ganoderma lucidum enjoys special veneration in Asia, where it has been used as a medicinal mushroom in traditional Chinese medicine for more than 4,000 years, making it one of the oldest mushrooms known to have been used in medicine. Lingzhi may possess anti-tumor, immunomodulatory and immunotherapeutic activities, supported by studies on polysaccharides, terpenes, and other bioactive compounds isolated from fruiting bodies and mycelia of this fungus (reviewed by R. R. Paterson[4] and Lindequist et al.[7]). It has also been found to inhibit platelet aggregation, and to lower blood pressure (via inhibition of angiotensin-converting enzyme[8]), cholesterol and blood sugar.[9] Laboratory studies have shown anti-neoplastic effects of fungal extracts or isolated compounds against some types of cancer. In an animal model, Ganoderma has been reported to prevent cancer metastasis,[10] with potency comparable to Lentinan from Shiitake mushrooms.[11] The mechanisms by which G. lucidum may affect cancer are unknown and they may target different stages of cancer development: inhibition of angiogenesis (formation of new, tumor-induced blood vessels, created to supply nutrients to the tumor) mediated by cytokines, cytoxicity, inhibiting migration of the cancer cells and metastasis, and inducing and enhancing apoptosis of tumor cells

The immunobiology of mushrooms. Borchers AT, Krishnamurthy A, Keen CL, Meyers FJ, Gershwin ME. Exp Biol Med (Maywood). 2008 Mar;233(3):259-76. Review. PMID: 18296732 doi: 10.3181/0708-MR-227

American Academy of Sleep Medicine. "Inflammation May Be Link Between Extreme Sleep Durations And Poor Health." ScienceDaily 7 February 2009. 25 February 2009 .

Fish oil and treatment of cancer cachexia. Giacosa A, Rondanelli M. Genes Nutr. 2008 Apr;3(1):25-8. PMID: 18850196

Prostaglandin E2 production and T cell function after fish-oil supplementation: response to antioxidant cosupplementation. Trebble TM, Wootton SA, Miles EA, Mullee M, Arden NK, Ballinger AB, Stroud MA, Burdge GC, Calder PC. Am J Clin Nutr. 2003 Sep;78(3):376-82. PMID: 12936918

Comparison of the effects of linseed oil and different doses of fish oil on mononuclear cell function in healthy human subjects. Wallace FA, Miles EA, Calder PC. Br J Nutr. 2003 May;89(5):679-89. PMID: 12720588

Limited effect of eicosapentaenoic acid on T-lymphocyte and natural killer cell numbers and functions in healthy young males. Miles EA, Banerjee T, Wells SJ, Calder PC. Nutrition. 2006 May;22(5):512-9. PMID: 16600816 doi:10.1016/j.nut.2005.11.011

Vitamin D and disease prevention with special reference to cardiovascular disease. Zittermann A. Prog Biophys Mol Biol. 2006 Sep;92(1):39-48. Epub 2006 Feb 28. Review. PMID: 1660034