Possible stimulation of anti-tumor immunity using repeated cold stress: a hypothesis

Abstract

BackgroundThe phenomenon of hormesis, whereby small amounts of seemingly harmful or stressful agents can be beneficial for the health and lifespan of laboratory animals has been reported in literature. In particular, there is accumulating evidence that daily brief cold stress can increase both numbers and activity of peripheral cytotoxic T lymphocytes and natural killer cells, the major effectors of adaptive and innate tumor immunity, respectively. This type of regimen (for 8 days) has been shown to improve survival of mice infected with intracellular parasite Toxoplasma gondii, which would also be consistent with enhanced cell-mediated immunity.Presentation of the hypothesisThis paper hypothesizes that brief cold-water stress repeated daily over many months could enhance anti-tumor immunity and improve survival rate of a non-lymphoid cancer. The possible mechanism of the non-specific stimulation of cellular immunity by repeated cold stress appears to involve transient activation of the sympathetic nervous system, hypothalamic-pituitary-adrenal and hypothalamic-pituitary-thyroid axes, as described in more detail in the text. Daily moderate cold hydrotherapy is known to reduce pain and does not appear to have noticeable adverse effects on normal test subjects, although some studies have shown that it can cause transient arrhythmias in patients with heart problems and can also inhibit humoral immunity. Sudden immersion in ice-cold water can cause transient pulmonary edema and increase permeability of the blood-brain barrier, thereby increasing mortality of neurovirulent infections.Testing the hypothesisThe proposed procedure is an adapted cold swim (5–7 minutes at 20 degrees Celsius, includes gradual adaptation) to be tested on a mouse tumor model. Mortality, tumor size, and measurements of cellular immunity (numbers and activity of peripheral CD8+ T lymphocytes and natural killer cells) of the cold-exposed group would be compared to those of control groups (warm swim and no treatment). Cold-water stress would be administered twice a day for the duration of several months.Implications of the hypothesisIf the hypothesis is supported by empirical studies and the method is shown to be safe, this could lead to the development of an adjunctive immunotherapy for some (non-lymphoid) cancers, including those caused by viral infections.

Perception of Patients with Cancer towards Support Management Services and Use of Complementary Alternative Medicine - a Single Institution Hospital-Based Study in Saudi Arabia

“…The potential of phytochemicals present in spices such as turmeric, red chilli, cloves, ginger, fennel, fenugreek, and black cumin in cancer prevention has been established (Aggarwal et al, 2008). There is accumulating evidence that repeated daily brief cold stress by hydrotherapy over many months can increase both numbers and activity of peripheral cytotoxic T lymphocytes and natural killer cells, the major effectors of adaptive and innate tumour immunity (Shevchuk and Radoja, 2007).…”

Self‐reported health and cardiovascular reactions to psychological stress in a large community sample: Cross‐sectional and prospective associations

“…There are precedents for positive associations between acute stress exposure and beneficial health outcomes. Acute exposure to moderate behavioral challenges has been associated with better health, mainly for immunological outcomes, and increased longevity in a number of recent laboratory animal studies (Arumugam, Gleichmann, Tang, & Mattson, 2006;Shevchuk & Radoja, 2007). This phenomenon is termed hormesis.…”

Prospective associations between cardiovascular reactions to acute psychological stress and change in physical disability in a large community sample

“…For example, exposure to acute mental stress in our own laboratory was associated with an enhanced antibody response to the influenza vaccine in women (Edwards et al, 2006). Similarly, in animals, short-term exposure to moderate behavioural challenges has been associated with better health, mainly for immunological outcomes, and increased longevity (Arumugam et al, 2006;Shevchuk and Radoja, 2007). Poorer immune function including a decreased ability to control infectious disease is characteristic of ageing and has been found to relate to morbidity and mortality in older age (Pawelec, 2006).…”