Stress Hormesis in Immune Function

 

Disclaimer

If you are a cancer patient or at risk and are seeking a cure outside the medical mainstream, this post is not for you and offers no cures or protective therapies. This post is written for researchers.

A Different way to Support the Immune System

Are more sophisticated immune-system training strategies the answer to preventing cancer? The acquired immune system is a learning system that has to learn what antigens to eliminate. Consider a person who experiences stress that suppresses their immune vigilance for a short time out of each year, after which the stress abates to let the immune function rebound. During suppression, whatever microcarcinomas happen to be present in the body run wild for a short time, thereby growing large enough for the immune surveillance function to easily detect them upon its return. They are then eliminated, of course, and the immune system learns something in the process, making it a more effective anti-cancer system going forward. The analogy here would be to a cat playing with a mouse it has caught. Since it is play, it is a learning activity; the cat is working on its game. 

This theory assumes that the early stages of antigen recognition contain a dose-dependent step that feeds a thresholding step. The antigen dose steadily rises as the cancer cells multiply. When the signal from the dose-dependent step is just under the threshold, the immune response can be half-on for prolonged periods because of an unphysiological negative feedback. This allows the microcarcinomas time to genetically diversify until they become uncontrollable when they eventually break out, provided the threshold never shows any large excursions. This post focuses on providing those large excursions.

Observational

Pre-civilization, human immune suppression may have happened regularly due to prolonged environmental challenges/“stressors” such as starvation, leading eventually to cannier immune systems and lower cancer rates than we now experience. (According to Selye's general adaptation model, which represents current thinking, the final exhaustion phase of stress adaptation is associated with impaired immune function, but with purely an increase in susceptibility to cancer. However, I prefer the interpretation that general stress adaptation is an analog of apoptosis, recapitulated at the whole-organism level. A component of apoptosis is autophagy, which overlaps with the response to starvation challenges. At the whole-organism level, immune suppression would be such a shared process. I include this to show how my theory can be framed without recourse to the construct “stress,” which may be protoscientific.)

The adaptive immune training paradigm articulated here agrees with the impression I have that cancer is a disease of modern lifestyles. Consistent with this, laboratory rats have a notable susceptibility to cancer, which can skew the results of cancer research, and they lead sheltered, indoor lives.

 

Experimental

The following article may be relevant: Coventry, B.J., Ashdown, M.L., Quinn, M.A. et al. CRP identifies homeostatic immune oscillations in cancer patients: a potential treatment targeting tool?. J Transl Med 7, 102 (2009). https://doi.org/10.1186/1479-5876-7-102

Summary and Future Directions

Hormesis is said to be present when a factor that is toxic in large doses is required in low doses for normal functioning. Is cancer a disease of too little stress? The matter may not be so simple. The possible stress benefit may be a function of the exact time-course of the stress. For example, it may be associated with a particular frequency of variation of experimentally imposed stress. The six-to-seven-day period of the cited immune oscillations would be an obvious pattern of stress variation to test.

Does everyone have the CRP cycle whether ill or not?

The week time period on which work and worship is organized may represent an unrecognized past cultural discovery of this cycle.

Photo by Nina Mercado on Unsplash