Interleukin-15 (IL-15) is a recently-discovered cytokine that is now generally considered a key immunomodulator. More recently however an international group of researchers have demonstrated that IL-15 also plays a role in metabolic disorders. Obesity, perhaps the most highly publicized of the metabolic disorders, is estimated to affect somewhere between 34 and 61 million people in the US alone, and in much of the developing world this incidence is increasing by about 1% per year. As a general guide, obesity increases the likelihood of death from all causes by 20%, and plays a major role in the development of coronary heart disease, stroke, diabetes and gall bladder disease. Thus the development of anorectics represents a priority of the drug development sector. We have recently highlighted ghrelin, one particularly promising target for obesity (click here to access our recent dossier “Ghrelin: The future of obesity therapeutics?”). IL-15 has now emerged as a second exciting target, inhibiting adipogenesis, lipid deposition, and PPAR gamma2 expression. In vivo, administration of IL-15 to normal rats, normal mice, and obese mice decreases white adipose tissue mass by as much as 30%, without effects on food intake. Alterations in IL-15 receptor subunit balance have also been described in the obese Zucker rat model. Much research related to obesity is also relevant to wasting conditions such as cachexia as well as age-associated sarcopenia and changes in lean:fat body composition. IL-15 represents a prime example in this respect since it is highly expressed at the mRNA level in skeletal muscle and has been shown to stimulate muscle protein synthesis and inhibit muscle protein degradation. Administration of IL-15 to tumour-bearing rats inhibits muscle wasting by inhibiting protein degradation. Taken together, these findings support the hypothesis that IL-15 may participate in a peripheral control loop influencing lean:fat body composition, such that muscle-derived IL-15 stimulates maintenance of muscle mass and inhibits fat deposition. To date, with the exception of Immunex's rIL-15, few IL-15 mimics have been developed despite their potential as treatments of a number of conditions including obesity and wasting associated with cancer, AIDs and aging. Thus, commercial interested in this target could reap considerable rewards.

Adapted from Alvarez et al, Biochim Biophys Acta 2002 Feb 15;1570(1):33-7

Interested in collaborating with this group? Contact leaddiscovery@bioportfolio.co.uk