Neuroimmunomodulation: a brief review. Can conditioning of natural killer cell activity reverse cancer and/or aging?

Modern scientific evidence of interactions among the nervous, endocrine, and immune systems dates from the late nineteenth century, although this concept was certainly known to the ancients in Asia, Europe, Africa, and the Americans. Within the past two decades, the mechanisms of these interactions, known today as neuroimmunomodulation (NIM), have been investigated, from the subcellular to the behavioral levels, using the modern tools of receptor and membrane physiology, biochemistry, pharmacology, immunology, chronobiology, and genetics. One of the best demonstrations of neural-immune interactions was classical (Pavlovian) conditioning of immune responses, first reported by Metal'nikov et al. at the Pasteur Institute in the 1920's. Within the past 10 years, my colleagues at the University of Alabama in Birmingham and the Gerontology Research Center in Italy, and I, in experiments with mice, demonstrated (a) a 3- to 39-fold enhancement of natural killer (NK) cell activity by conditioning; (b) reversal of an otherwise fatal cancer (myelo-MOPC-104 E) by perinoculation conditioning ; and (c) that very old animals can be similarly conditioned to increase, many fold, their NK activity in the absence of an antigen. NK cells are among the body's first-line defenses against cancer and viral infections. Research on NIM and its mechanisms is growing exponentially; indeed, it may be the fastest growing field in biomedical sciences. (The International Society for NIM, founded only a few years ago, now has active members in 40 countries.) This revolution in the basic sciences will undoubtedly lead to a corresponding revolution in clinical practice and, most importantly, in the area of preventive medicine.