interleukin 15

[oswaldosalcedo]

opening a thread about interleukin 15.

[Titan1]

studies. IL-15 sounds actually as a safer alternative of IGF-1 for those concerned about cancer risks:

Interleukin-15: a novel anabolic cytokine for skeletal muscle.

Quinn LS, Haugk KL, Grabstein KH.

Geriatric Research, Education, and Clinical Center, American Lake VA Medical Center, Tacoma, WA 98493, USA.

Interleukin-15 (IL-15) is a recently discovered growth factor which is highly expressed in skeletal muscle. In order to determine a functional role for IL-15 in skeletal myogenesis, the effects of IL-15 on myoblast proliferation and muscle-specific myosin heavy chain (MHC) expression were analyzed using the mouse C2 skeletal myogenic cell line and primary fetal bovine skeletal myogenic cultures. IL-15 had no effect on [3H]thymidine incorporation, nor on the rate of myoblast differentiation, assessed by anti-MHC immunocytochemical staining, in either type of culture. However, Western blot analyses revealed that IL-15 used at concentrations of 10 or 100 ng/ml increased MHC accumulation five-fold in C2 myoblast cultures and 2.5-fold in primary bovine myogenic cultures. Moreover, C2 myotubes formed in the presence of IL-15 appeared larger than controls. These findings indicate IL-15 can stimulate differentiated myocytes and muscle fibers to accumulate increased amounts of contractile proteins. Well-fused primary bovine myogenic cultures treated with the mitotic inhibitor aphidicolin, then administered IL-15 and/or the anabolic growth factor insulin -like growth factor-I (IGF-I), were analyzed for MHC accumulation using Western blots. IL-15 used at 10 ng/ml doubled MHC accumulation and was as effective as IGF-I used at 10 or 100 ng/ml. IL-15 and IGF-I used together increased MHC accumulation close to five-fold, indicating these two factors can act additively on muscle fibers. These findings indicate IL-15 affects parameters associated with skeletal muscle fiber hypertrophy, and suggest that IL-15 may be a novel anabolic agent to increase skeletal muscle mass.

PMID: 7628408 [PubMed - indexed for MEDLINE]
(*)

Association of interleukin-15 protein and interleukin-15 receptor genetic variation with resistance exercise training responses.

Riechman SE, Balasekaran G, Roth SM, Ferrell RE.

Department of Human Genetics, Graduate School of Public Health, University of Pittsburgh, PA 15260, USA. [email protected]

Interleukin-15 (IL-15) is an anabolic cytokine that is produced in skeletal muscle and directly affects muscle anabolism in animal and in vitro models. The contribution of IL-15 variability in muscle responses to 10 wk of resistance exercise training in young men and women was examined by measuring acute and chronic changes in IL-15 protein in plasma and characterizing genetic variation in the IL-15 receptor-alpha gene (IL15RA). Participants trained 3 days a week at 75% of one repetition maximum, performing three sets (6-10 repetitions) of 13 resistance exercises. Plasma IL-15 protein was significantly increased (P < 0.05) immediately after acute resistance exercise but did not change with training and was not associated with variability in muscle responses with training. A single nucleotide polymorphism in exon 7 of IL15RA was strongly associated with muscle hypertrophy and accounted for 7.1% of the variation in regression modeling. A polymorphism in exon 4 was also independently associated with muscle hypertrophy and accounted for an additional 3.5% of the variation in hypertrophy. These results suggest that IL-15 is an important mediator of muscle mass response to resistance exercise training in humans and that genetic variation in IL15RA accounts for a significant proportion of the variability in this response.

PMID: 15531573 [PubMed - in process]

Overexpression of interleukin-15 induces skeletal muscle hypertrophy in vitro: implications for treatment of muscle wasting disorders.

Quinn LS, Anderson BG, Drivdahl RH, Alvarez B, Argiles JM.

Division of Gerontology and Geriatric Medicine, University of Washington, Seattle 98195, USA. [email protected]

Interleukin-15 (IL-15) is a novel anabolic factor for skeletal muscle which inhibits muscle wasting associated with cancer (cachexia) in a rat model. To develop a cell culture system in which the mechanism of the anabolic action of IL-15 on skeletal muscle could be examined, the mouse C2 skeletal myogenic cell line was transduced with a retroviral expression vector for IL-15 and compared to sister cells transduced with a control vector. Overexpression of IL-15 induced fivefold higher levels of sarcomeric myosin heavy chain and alpha-actin accumulation in differentiated myotubes. Secreted factors from IL-15-overexpressing myogenic cells, but not from control cells, induced increased myofibrillar protein accumulation in cocultured control myotubes. IL-15 overexpression induced a hypertrophic myotube morphology similar to that described for cultured myotubes which overexpressed the well-characterized anabolic factor insulin-like growth factor-I (IGF-I). However, in contrast to IGF-I, the hypertrophic action of IL-15 on skeletal myogenic cells did not involve stimulation of skeletal myoblast proliferation or differentiation. IL-15 induced myotube hypertrophy at both low and high IGF-I concentrations. Furthermore, in contrast to IGF-I, which stimulated only protein synthesis under these culture conditions, IL-15 both stimulated protein synthesis and inhibited protein degradation in cultured skeletal myotubes. These findings indicate that IL-15 action on skeletal myogenic cells is distinct from that of IGF-I. Due to the ability of IGF-I to stimulate cell division and its association with several forms of cancer, controversy exists concerning the advisability of treating cachexia or age-associated muscle wasting with IGF-I. Administration of IL-15 or modulation of the IL-15 signaling pathway may represent an alternative strategy for maintaining skeletal muscle mass under these conditions.

PMID: 12372339 [PubMed - indexed for MEDLINE]

(* You can get the full text of this which is very interesting. Look at the graph when stacked with IGF-1. From the conclusions:
"The precise roles, mode of action, and regulation of expression of IL15 in skeletal muscle tissue remain to be defiid Unlike other anabolic agents such as anabolic steroids , GH, or IGF, which have multiple effects on a wide range of tissues, the effects of IL15 may be more tissue-specific. IL15 may therefore prove to be a useful agent for stimulating skeletal muscle growth or reversing skeletal muscle atrophy.")
__________________

[Titan1]

IL-15 Activates Telomerase and Minimizes Telomere Loss and May Preserve the Replicative Life Span of Memory CD8+ T Cells In Vitro.

Li Y, Zhi W, Wareski P, Weng NP.

Laboratory of Immunology, National Institute on Aging, National Institutes of Health, Baltimore, MD 21224.

The preservation of the replicative life span of memory CD8(+) T cells is vital for long-term immune protection. Although IL-15 plays a key role in the homeostasis of memory CD8(+) T cells, it is unknown whether IL-15 regulates the replicative life span of memory CD8(+) T cells. In this study, we report an analysis of telomerase expression and telomere length in human memory phenotype CD8(+) T cells maintained by IL-15 in vitro. We demonstrate that IL-15 is capable of activating telomerase in memory CD8(+) T cells via Jak3 and PI3K signaling pathways. Furthermore, IL-15 induces a sustained level of telomerase activity over long periods of time, and in turn minimizes telomere loss in memory CD8(+) T cells after substantial cell divisions. These findings suggest that IL-15 activates stable telomerase expression and compensates telomere loss in memory phenotype CD8(+) T cells, and that telomerase may play an important role in memory CD8(+) T cell homeostasis.




A novel role of IL-15 in early activation of memory CD8+ CTL after reinfection.

Yajima T, Nishimura H, Sad S, Shen H, Kuwano H, Yoshikai Y.

Division of Host Defense, Medical Institute of Bioregulation, Kyushu University, Fukuoka, Japan. [email protected]

A rapid induction of effector functions in memory T cells provides rapid and intensified protection against reinfection. To determine potential roles of IL-15 in early expansion and activation of memory CD8+ T cells in secondary immune response, we examined the cell division and cytotoxicity of memory CD8+ T cells expressing OVA(257-264)/Kb-specific TCR that were transferred into IL-15-transgenic (Tg) mice, IL-15 knockout (KO) mice, or control C57BL/6 mice followed by challenge with recombinant Listeria monocytogenes expressing OVA (rLM-OVA). In vivo CTL activities and expression of granzyme B of the transferred CD8+ T cells were significantly higher in the IL-15 Tg mice but lower in the IL-15 KO mice than those in control mice at the early stage after challenge with rLM-OVA. In contrast, there was no difference in the cell division in IL-15 Tg mice and IL-15 KO mice compared with those in control mice. In vivo administration of rIL-15 conferred robust protection against reinfection via induction of granzyme B in the memory CD8+ T cells. These results suggest that IL-15 plays an important role in early activation of memory CD8+ T cells.






Interleukin-2, interleukin-15, and their roles in human natural killer cells.

Becknell B, Caligiuri MA.

Medical Scientist Program, USA.

Natural killer (NK) cells are CD56(+)CD3(-) large granular lymphocytes that constitute a key component of the human innate immune response. In addition to their potent cytolytic activity, NK cells elaborate a host of immunoregulatory cytokines and chemokines that play a crucial role in pathogen clearance. Furthermore, interactions between NK and other immune cells are implicated in triggering the adaptive, or antigen-specific, immune response. Interleukin-2 (IL-2) and IL-15 are two distinct cytokines with partially overlapping properties that are implicated in the development, homeostasis, and function of NK cells. This review examines the pervasive effects of IL-2 and IL-15 on NK cell biology, with an emphasis on recent discoveries and lingering challenges in the field.

PMID: 15705423 [PubMed - in process]




Synergy of IL-21 and IL-15 in regulating CD8+ T cell expansion and function.

Zeng R, Spolski R, Finkelstein SE, Oh S, Kovanen PE, Hinrichs CS, Pise-Masison CA, Radonovich MF, Brady JN, Restifo NP, Berzofsky JA, Leonard WJ.

Laboratory of Molecular Immunology, National Heart, Lung, and Blood Institute, National Institutes of Health, Bethesda, MD 20892, USA.

Interleukin (IL)-21 is the most recently recognized of the cytokines that share the common cytokine receptor gamma chain (gamma(c)), which is mutated in humans with X-linked severe combined immunodeficiency. We now report that IL-21 synergistically acts with IL-15 to potently promote the proliferation of both memory (CD44high) and naive (CD44low) phenotype CD8+ T cells and augment interferon-gamma production in vitro. IL-21 also cooperated, albeit more weakly, with IL-7, but not with IL-2. Correspondingly, the expansion and cytotoxicity of CD8+ T cells were impaired in IL-21R-/- mice. Moreover, in vivo administration of IL-21 in combination with IL-15 boosted antigen-specific CD8+ T cell numbers and resulted in a cooperative effect on tumor regression, with apparent cures of large, established B16 melanomas. Thus, our studies reveal that IL-21 potently regulates CD8+ T cell expansion and effector function, primarily in a synergistic context with IL-15.

Note: CD8+ T cells are the same thing as cytotoxic t cells which play a large role in killing intracellular infections and releasing other important cytokines, stimulating an immune response.

[j martini]

I posted this a while ago it was written by Arthur L. Rea im Muscular Development.
The price puts it out of reach for 99% of people.


Interluekin 15 is a cytokine thats highly expressed in skeletal muscle. Cell structure studies have shown that IL-15 may have an important role in muscle fiber growth and anabolism. However dat concerning the metabolic effects of this cytokine in vivo are lacking.

In a brief study, IL-15 was administered for seven days to adult rats. Though it did significantly affect both protein synthesis(anabolism) and degradation(catabolism) in favour of growth, the amazing result was in the effects it had upon adipose tissue and blood lipids. After only seven days of administration, the adult rats realized a 33percent decrease in white adipose tissus(bodyfat) and a 25 percent decrease in circulating triglycerides.

IL-15 on paper seems to be more effectual than igf1 and far safer, even though together they are 5 times more anabolic than either alone.

There is one downfall however a 30 day protocol of IL-15 can cost as much as $20,000. Although im sure with time the price will drop.

[oswaldosalcedo]

price:
Recombinant Human Interleukin-15 rHuIL-15 1mg $ 3550

dose: i dont know!

100 mcg daily ? 50 mcg ? 200 mcg?

one month?
two month?

i read that markus ruhl has used it.
coleman sure !

and............... is a citokyne.

other info:
1. Anabolic Master. Het allernieuwste en heftigste middel. Anabolica Discussions Nederland, 12-11-2001.
2. Brock Strasser. Strasseroids, Lutalyse? More like Loserlyse. T-Mag, nr. 111, 30-6-2000.
3. Brian Batcheldor. The S-Files. T-Mag, nr. 143, 9-2-2001.
4. Dokter Bert. Mailbericht aan Ergogenics.
5. Quinn LS, Haugk KL, Grabstein KH. Interleukin-15: a novel anabolic cytokine for skeletal muscle. Endocrinology 1995 Aug;136(8):3669-72. [PubMed]
6. Quinn LS, Anderson BG, Drivdahl RH, Alvarez B, Argiles JM. Overexpression of interleukin-15 induces skeletal muscle hypertrophy in vitro: implications for treatment of muscle wasting disorders. Exp Cell Res 2002 Oct 15;280(1):55-63. [PubMed]
7. Carbo N, Lopez-Soriano J, Costelli P, Alvarez B, Busquets S, Baccino FM, Quinn LS, Lopez- Soriano FJ, Argiles JM. Interleukin-15 mediates reciprocal regulation of adipose and muscle mass: a potential role in body weight control. Biochim Biophys Acta 2001 Apr 3;1526(1):17-24. [PubMed]
8. Carbo N, Lopez-Soriano J, Costelli P, Busquets S, Alvarez B, Baccino FM, Quinn LS, Lopez- Soriano FJ, Argiles JM. Interleukin-15 antagonizes muscle protein waste in tumour-bearing rats. Br J Cancer 2000 Aug;83(4):526-31. [PubMed]
9. Baker CH, Abel FL. Macro- and microcirculatory effects of IL-15. Shock 1995 Oct;4(4):307-10. [PubMed]
10. Fehniger TA, Suzuki K, VanDeusen JB, Cooper MA, Freud AG, Caligiuri MA. Fatal leukemia in interleukin-15 transgenic mice. Blood Cells Mol Dis 2001 Jan-Feb;27(1):223-30. [PubMed]
11. Choi KD, Lillehoj HS, Song KD, Han JY. Molecular and functional characterization of chicken IL-15. Dev Comp Immunol 1999 Mar-Apr;23(2):165-77. [PubMed]

[cyflex]

Has anybody heard/know about the dosage of IL-15
I read (dont remeber where) that is 0.2mcg/lb of LBM

peace
cyflex

[oswaldosalcedo]

40 to 60 mcg, then.
thanks.
(which would be the place "website"?)

[alwayson]

you guys are crazy bastards