relin inhibited the production of HMGB-1 by activated macrophages,207 which may explain its beneficial action in sepsis and other inflammatory conditions.208,209 PubMed ID:http://www.ncbi.nlm.nih.gov/pubmed/19836572 These results suggest that ghrelin infusion could be of significant benefit in lupus, RA, and other autoimmune diseases not only by its direct action of the production of proinflammatory cytokines but also by its ability to stimulate vagus that has anti-inflammatory actions. Conclusion Lupus, RA, and other autoimmune diseases are chronic inflammatory conditions that often have acute and intermittent inflammatory episodes. It is recommended that some of these suggested approaches could be performed in combination with the currently available therapeutic drugs. For example, GIK regimen, ethylpyruvate, lipid-enriched albumin, VNS, LXs, resolvins, protectins and their synthetic analogs, and ghrelin could be tried in combination with nonsteroidal anti-inflammatory compounds, chloroquine, corticosteroids, d-penicillamine, sulfasalazine, methotrexate, anti-TNF antibodies, and immunosuppressive drugs. Another option that could be investigated is the use of anti-TNF- and other biologics in combination with EP, ghrelin, PUFAs, LXs, resolvins and protectins, and insulin and be used as parenteral infusion. All these permutations and combinations need to be tried both in the animal models of various autoimmune diseases and other inflammatory conditions and in the clinic before knowing which therapeutic approach is of significant benefit to these patients. With such an approach, one can measure various plasma tissue factors, as shown in Acknowledgment Dr UN Das was in receipt of the Ramalingaswami fellowship from the Department of Biotechnology during the tenure of this study. Disclosure The author reports no conflicts of interest in this work. Sirtuins are a highly conserved family of proteins. The silent information regulator 2 gene was first described in budding yeast as a regulator of chromatin structure and named MAR1 . A set of four genes, SIR14 described later, replaced the name “MAR” with “SIR”. Subsequently, SIR2 homologues were identified in bacteria, plants, and mammals, representing a large family of highly conserved proteins called “sirtuins”. Sirtuins belong to class III histone deacetylase family of enzymes. There are 7 mammalian sirtuins with distinct protein structure, varied subcellular location, and unique functional properties. The requirement for NAD+ as a cosubstrate for SIR2 deacetylase activity suggests that sirtuins may have developed as energy sensors and the redox state of cells. Metabolism is known to influence aging in rodents and a number of other species of organisms. Several lines of evidence suggest that benefits of calorie restriction are mediated through sirtuins. The most convincing link between aging and sirtuins was established after the effects of aging on NAD+ were studied. In addition to its role as a cofactor in many enzymatic processes, NAD+ regulates key metabolic processes. Sirtuins are NAD+ sensors. SIRT1 and SIRT6 are known aging related sirtuins. Evidence suggests that NAD+ levels are decreased in aging; NAD+ replenishment in aged mice restores mitochondrial homeostasis in a SIRT1 dependent manner. SIRT6 deficient mice show signs of accelerated aging and early death from hypoglycemia. Inflammation defends against 1235481-90-9 severe stress responses and if successful must resolve. SIRT1, known as a major 2 metabolic regulator, epigenetically reprograms infl