Relazione presentata dal Dott.Ascanio Polimeni al congresso internazionale di medicina antiaging di Monaco-aprile 2013

IL6 and AGING: the UGLY, the GOOD and the INDIFFERENT.

The human interleukin IL-6 was originally cloned in 1986. In 1993, William Ershler, in his article "IL-6: A Cytokine for Gerontologists," indicated IL-6 as one of the main signaling pathways modulating the complex relationship between aging and chronic morbidity. Over the last 12 years, our understanding of the role of IL-6 in human physiology and pathology has substantially grown, although some of the questions originally posed by Ershler are still debated.Interleukin-6 (IL-6) is a multifunctional cytokine regulating humoral and cellular responses and playing a central role in inflammation and tissue injury. Its effects are mediated through interaction with its receptor complex, IL-6Rβ (also known as gp130). It plays an important role in the pathogenesis of coronary artery disease and large quantities of IL-6 are found in human atherosclerotic plaques. IL-6 levels positively correlate with higher all-cause mortality, unstable angina, left ventricular dysfunction, propensity to diabetes and its complications, hypertension, obesity and several types of cancer. IL-6 levels augmentation demonstrates a remarkable parallel with another biomarkers reflecting harmful processes, like tumor necrosis factor alpha, interleukins 8 and 18, YKL-40, C reactive protein and resistin.This overproduction of inflammatory mediators is  also expression of disimmuneaging and is named also inflammaging or low grade inflammation  that’s  considered by worlwide scientists  the mother of aging and aging related diseases like dementia,cvd,osteoporosis,cancer,diabesity,sarcopenia and sarcopenic obesity. Due to these facts, IL-6 has been classified as a noxious interleukin. Nonetheless, there are several facts that challenge this usually accepted point of view. Since IL-6 has also anti-inflammatory activity, it seems reasonable to assume that favorable aspects exist. These aspects are two: 1. protection against bacterial infections, inactivating proinflammatory mediators, mitigating the course of septic shock and inducing the production of cortisol; in general a global positive effect  due to a concomitant proinflammatory  and antinflammatory effect is found in acute inflammation or trauma.  2. influence on insulin sensitivity during exercise; this aspect is even more important. During exercise IL-6 is synthesized and released by muscles, with enhanced insulin action immediately at early recovery. Skeletal muscle may be considered as an endocrine organ; contracting muscles produce IL-6 and release it into the blood exerting its effects on other organs. The increase in circulating levels of IL-6 after exercise is consistent and proportional to exercise duration, intensity, muscle mass involved and endurance capacity. Thus, the fascinating possibility that the plenteous beneficial health effects of exercise could be ultimately mediated by IL-6 merits further elucidation. While for some aspects of aging process like cvd,sarcopenia,osteoporosis and dementia IL 6 accumulation  seems to be one of the main negative players,the modern vision on the effects of IL6 on insulin  resistence,m.s.,diabesity , obesity  seem to be protective  rather then deleterious as thought in the past. It’s also possible  also  that IL 6   could be the effect and not  the cause of some diseases. Infact, Interleukins were termed "good" or "bad", probably due to a tendency to see things in black and white, with no gray area in between. Calling IL-6 "a molecule with both beneficial and destructive potentials" would be a more equitable approach. In the literary creatures of Dr. Jekyll and Mr. Hyde, a good and an evil personality are found in the same individual. IL-6 playing the role of Dr. Jekyll is emerging; the time for the change of  absolutely negative thinking about IL6 effects is coming.