itamin D and autoimmunity: new aetiological and therapeutic considerations.
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Th1/Th2 balance: the hypothesis, its limitations, and implications for health and disease.
Kidd P.
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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.