Overview

Cytokines are implied in polymyositis/dermatomyositis (PM/DM) pathogenesis. Our aim is to evaluate the serum levels of interleukin-15 (IL-15), soluble receptors for IL-2 (sIL-2R) , TNF-alpha type 1 receptor (sTNF-R1) and all other relevant receptors expressd in PM/DM patients and their relation to disease activity and clinical symptoms.
 

IL-15 receptor

Interleukin-15 (IL-15) is a proinflammatory cytokine with pleiotropic activity. It stimulates the proliferation and activation of T cells, macrophages, CD5 memory lymphocytes and cytotoxic CD8 lymphocytes, proliferation of myoblasts, endothelial cells and many others . The IL-15-specific receptor is composed of 3 subunits: alpha, beta and gamma. The latter is shared with IL-2 and other cytokines (IL-4, IL-7, IL-9 and IL-21), which explains their similar effects. IL-15 seems to have the widest activity spectrum of the whole IL-2 family. Both, IL-15 receptors and IL-15 mRNA, were found in many non-immunological tissues and cells (placenta, muscle, kidney, heart, fibroblasts and myoblasts) .(1)

The role of IL-15 in the pathogenesis of inflammatory, autoimmune disease like rheumatoid arthritis has been demonstrated, but data explaining the role of IL-15 in the pathogenesis of PM/DM are limited (1,2)

It seems that this IL-15 receptor is always present, but further trials needs to be done.
 

Literature review

IL-15 seems to be the ideal candidate for the factor sustaining the inflammation in these rare diseases, as it is not only produced by myoblasts, but also its receptor has been found in muscle tissue . The increased synthesis of IL-15 by myoblasts isolated from PM/DM patients, but not from healthy controls, was shown by Siagura et al.(2).

We confirm the existence of higher levels of IL-15 in PM/DM patients compared to healthy controls as was previously reported by Suzuki et al. [3] Moreover, we found a correlation between disease activity and IL-15 serum concentration. Not all measured parameters achieved statistical significance, possibly due to the relatively small number of patients included in this studies. Suzuki et al. found higher levels of IL-15, IL-2 and tnf receptors in patients with various inflammatory connective tissue diseases and ILD [3]. We did not demonstrate a similar phenomenon in our group, but our study selected only PM/DM patients with the possible domination of muscle IL-15 production. Our results add to previous observations and give further evidence in favour of a stimulating role of IL-15 in these diseases.

We noted higher levels of sTNF-R1 and sIL2-R in the patients in active disease. High sIL2-R levels have been found in many inflammatory and neoplasmatic conditions, often correlating with disease activity and determining prognosis [4]. We demonstrated a correlation between sIL2-R levels and disease activity, but not with any specific clinical parameter. Samsonov et al. [5] failed to notice any correlation between myositis activity and serum concentrations of sIL2-R; however, they did find such an association with ESR.

The results of sTNF-R1 levels are consistent with previous reports [6]. Other authors found correlation with disease activity not only for sTNF-R1 but also for sTNF-R2 [6]. Extremely high levels of the receptor found in subjects with neoplasm-induced DM are interesting but due to the small number of patients and possible biases, no firm conclusions can be drawn. However, since high levels of sTNF-R1 were observed in cancer patients without inflammatory myopathies, it is not clear whether this parameter can be used as a differentiating factor between primary DM and cancer-induced DM [7,8].

Relevance

High concentration of IL-15 as well as sIL2-R and sTNF-R1 in active patients with DM/PM provides additional evidence for a broad activation of inflammatory response. Further studies are needed to explain the mechanisms driving these diseases. High level sTNF-R1 in cases of neoplasm-induced PM/DM requires confirmation in the future studies.

 

Foot notes 

1. Fehniger TA, Interleukin 15: biology and relevance to human disease. Blood 97:14–32PubMedCrossRef
2. Sugiura T.Increased IL-15 production of muscle cells in polymyositis and dermatomyositis. Int Immunol 14:917–924PubMedCrossRef
3. Suzuki J, Serum levels of interleukin 15 in patients with rheumatic diseases. J Rheumatol 28:2389–2391PubMed
4. Elkayam O, Yaron I, Shirazi I, Yaron M, Caspi D (2000) Serum levels of IL-10, IL-6, IL-1ra, and sIL-2R in patients with psoriatic arthritis. Rheumatol Int 19:101–105PubMedCrossRef
5. Chrobak L, Serum soluble IL-2 receptor as a reliable and noninvasive marker of disease activity in patients with hairy cell leukemia. Neoplasma 43:321–325PubMed
6. Samsonov MY, Elevated serum levels of neopterin in adult patients with polymyositis/dermatomyositis. Br J Rheumatol 36:656–660PubMedCrossRef
7. Bohan A, Polymyositis and dermatomyositis (first of two parts). N Engl J Med 292:344–347PubMedCrossRef
8. Kurowska M, Fibroblast-like synoviocytes from rheumatoid arthritis patients express functional IL-15 receptor complex: endogenous IL-15 in autocrine fashion enhances cell proliferation and expression of Bcl-x(L) and Bcl-2. J Immunol 169:1760–1767PubMed