The feedsideward of cephalo-adrenal immune interactions.

The feedsideward phenomenon is the interaction of three or more rhythmic physiological entities by a diversified spectrum of rhythms that constitute a rhythmic network. These rhythmic units are: a) the modulator, b) the actor, c) the reactor and d) the integrative unity. Rhythmic interactions are characterized by an alternating sequence of algorithmically predictable effects of attenuation, no effect, and stimulation occurring in different frequencies. The basis of this phenomenon was determined from experimental evidence derived from cephalo-adrenal ex vivo studies. Internal phase-shift studies allow the demonstration ex vivo of a collateral hierarchy of rhythmic neuro-endocrine interactions as alpha, beta, gamma and delta rhythms. Linear least squares analyses describe and quantify circadian (alpha, beta and gamma) and infradian (delta) rhythms in the original series and the differences in responses [beta-alpha] and [gamma-delta]. These spontaneous and response rhythms reveal a collateral neuro-endocrine hierarchy and validate a pineal feedsideward phenomenon. Circadian-infradian murine rhythmic intermodulations are demonstrated in the epithelial corneal mitosis; brain neurosteroids and pineal melatonin content. A circadian rhythm in pineal melatonin content in female B6D2F1 mice and the chronomodulating action of melatonin + ACTH upon adrenal corticosterone production are confirmed. A chronopilot ex vivo study "suggests" that melatonin chronomodulates mouse aldosterone production. In a second chronopilot study, HrIL-2 chronomodulates rat corticosterone production ex vivo. Feedsidewards in vivo were seen in the chronomodulation of tumor-host balance occurring after melatonin, IL-2, cefodizime, and cyclosporine treatments that enhanced or delayed tumor growth and survival time of tumor-bearing mice.