GB-Marble
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we've got a new drug showing up on the bodybuilding horizon, interleukin-15. it has generated a lot of excitement because of several in vitro -- think tissue in petrie dish -- studies demonstrating tremendous muscular hypertrophy. there's no doubt it's extremely effective. it's already available from several research companies, and some people have already hurt themselves badly using it. this post discusses the basics of what it is, how it might be useful, and why it isn't right now.
interleukin-15 is not ready for primetime similar to how igf-i alone wasn't ready until modified to the lr3igf-i analog, and will lead to muscle loss and other very bad outcomes unless you use small amounts. something that makes your body produce it may be a good bodybuilding drug someday in small doses. IL-15 isn't a good bodybuilding drug right now.
the interleukin family is not really a set of hormones, but a set of cytokines instead. it's produced locally for the most part and it is really much more specific to immune system function, not muscle growth or cell growth in general. this is different from most of the muscle-building drugs we take, which are or emulate hormones and work more systemically.
il-15 in particular is very similar to il-2 and both seem to heavily modulate the attack functions of the immune response. its major systemic job is more to stimulate the growth of many different immune cells, including T, B, and TIL's. it also can be used to trigger and localize these attacks; if it's expressed in a given tissue killer NK cells will be more likely to come to and attack it.
in addition to these properties, though, it does indeed seem to act directly on skeletal muscle. this is really weird and wasn't expected. there's no obvious explanation for why it would be this way. it only leads to myotube hypertrophy (similar to androgens) and not myoblast proliferation or differentiation (similar to igf-i).
http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=14499665
http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=12372339
it does seem to be make up a good part of the amount of "genetic potential" people have. studies have found variations in its production correlate highly with the degree to which people respond to resistance training:
http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=15531573
the $1,000 question is whether this translates to meaning that really high levels would mean a lot more muscle growth. the answer is "no, because you're going to make your body kill itself and/or your own muscle." using too much systemic IL-15 will cause random autoimmune diseases, such as arthritis, type 1 diabetes, or lupus. using too much of a drug targeted at intramuscular IL-15 in particular for too long would probably give you either myasthenia gravis or some form of idiopathic inflammatory myopathy, neither of which is very conducive to moving, and have 5-year mortality rates above 20%. essentially, the high levels of il-15 will cause those killer immune cells to viciously attack your muscle.
http://rheumatology.oupjournals.org/cgi/content/full/40/8/876
http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=14611115
http://intimm.oupjournals.org/cgi/content/full/14/8/917
so, small, targeted amounts may help, but you have to be very careful. i would never recommend systemic use, particularly when combined with insulin. the combination of these two will very likely cause your body to initiate thermonuclear warfare on your own pancreas leading to bad type 1 diabetes. a few people have already done this to themselves. there's also no guarantee it'll seep into muscle cells very well once it's in your system broadly. it has an extremely short serum half-life to boot.
http://www.jbc.org/cgi/content/full/272/4/2312
if you were determined to go ahead anyway, it would be preferable to use signalling cytokines or a monoclonal antibody similar to mAb35, both of which would trigger local intramuscular IL-15 production. this would be more targeted and interesting than direct systemic administration of il-15, which led to no net growth of muscle in healthy rats. to the contrary, it has been demonstrated in vivo that long-term use of this antibody can actually lead to permanent wasting of muscle because the immune system beats it to shreds. the one in which there was growth was in those with tumors, and given il-15's role in the immune system, this is a very bad population to look at whether it's useful for muscle growth in bodybuilders. it is a great model for cancer patients where it could certainly be useful.
http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=11585642
http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=11287118
http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=12690362&dopt=Abstract
http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=10945502
if something stimulating muscular IL-15 production is ever used by bodybuilding, proper dosage will be critical to making it work, and it'll be pretty risky. it may be useful someday though.
interleukin-15 is not ready for primetime similar to how igf-i alone wasn't ready until modified to the lr3igf-i analog, and will lead to muscle loss and other very bad outcomes unless you use small amounts. something that makes your body produce it may be a good bodybuilding drug someday in small doses. IL-15 isn't a good bodybuilding drug right now.
the interleukin family is not really a set of hormones, but a set of cytokines instead. it's produced locally for the most part and it is really much more specific to immune system function, not muscle growth or cell growth in general. this is different from most of the muscle-building drugs we take, which are or emulate hormones and work more systemically.
il-15 in particular is very similar to il-2 and both seem to heavily modulate the attack functions of the immune response. its major systemic job is more to stimulate the growth of many different immune cells, including T, B, and TIL's. it also can be used to trigger and localize these attacks; if it's expressed in a given tissue killer NK cells will be more likely to come to and attack it.
in addition to these properties, though, it does indeed seem to act directly on skeletal muscle. this is really weird and wasn't expected. there's no obvious explanation for why it would be this way. it only leads to myotube hypertrophy (similar to androgens) and not myoblast proliferation or differentiation (similar to igf-i).
http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=14499665
http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=12372339
it does seem to be make up a good part of the amount of "genetic potential" people have. studies have found variations in its production correlate highly with the degree to which people respond to resistance training:
http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=15531573
the $1,000 question is whether this translates to meaning that really high levels would mean a lot more muscle growth. the answer is "no, because you're going to make your body kill itself and/or your own muscle." using too much systemic IL-15 will cause random autoimmune diseases, such as arthritis, type 1 diabetes, or lupus. using too much of a drug targeted at intramuscular IL-15 in particular for too long would probably give you either myasthenia gravis or some form of idiopathic inflammatory myopathy, neither of which is very conducive to moving, and have 5-year mortality rates above 20%. essentially, the high levels of il-15 will cause those killer immune cells to viciously attack your muscle.
http://rheumatology.oupjournals.org/cgi/content/full/40/8/876
http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=14611115
http://intimm.oupjournals.org/cgi/content/full/14/8/917
so, small, targeted amounts may help, but you have to be very careful. i would never recommend systemic use, particularly when combined with insulin. the combination of these two will very likely cause your body to initiate thermonuclear warfare on your own pancreas leading to bad type 1 diabetes. a few people have already done this to themselves. there's also no guarantee it'll seep into muscle cells very well once it's in your system broadly. it has an extremely short serum half-life to boot.
http://www.jbc.org/cgi/content/full/272/4/2312
if you were determined to go ahead anyway, it would be preferable to use signalling cytokines or a monoclonal antibody similar to mAb35, both of which would trigger local intramuscular IL-15 production. this would be more targeted and interesting than direct systemic administration of il-15, which led to no net growth of muscle in healthy rats. to the contrary, it has been demonstrated in vivo that long-term use of this antibody can actually lead to permanent wasting of muscle because the immune system beats it to shreds. the one in which there was growth was in those with tumors, and given il-15's role in the immune system, this is a very bad population to look at whether it's useful for muscle growth in bodybuilders. it is a great model for cancer patients where it could certainly be useful.
http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=11585642
http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=11287118
http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=12690362&dopt=Abstract
http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=10945502
if something stimulating muscular IL-15 production is ever used by bodybuilding, proper dosage will be critical to making it work, and it'll be pretty risky. it may be useful someday though.
