Overview

 Interleukin-33 is a member of the IL-1 family of cytokines, which plays its role after binding to its specific cell membrane receptor. Involvement of IL-33 in certain acute and chronic inflammatory and auto-immune diseases has been previously reported. Interleukin-33 is found in the nuclei of the producing cells like epithelial and smooth muscle cells and is widely expressed in tissues, yet specifically located within cell types such as epithelial linings and smooth muscle cells (1). The biological effect of the presence of IL-33 in the nucleus is not well recognized, and at least two different roles have been explained. First, storage of IL-33 in the nucleus may act as an alarm in, which is released after cell destruction to modify the immune response and the surrounding tissue. Second, IL-33 was found to participate with heterochromatin and it was proposed that nuclear IL-33 negatively alters gene transcription by an intracrine, non-IL-33 receptor-mediated pathway by a yet to be known molecular mechanism. Therefore, IL-33 is a dual function cytokine, which acts as an intracellular modulator of gene expression and also as an alarm in agent that begins inflammation in response to cellular necrosis (2).

Interleukin-33 as a pro-inflammatory cytokine can mediate various immune responses. Previous studies have shown increased serum levels of IL-33 in patients with rheumatoid arthritis compared to healthy control subjects (3). It seems that synovial fibroblasts are one of the major sources of IL-33 in RA, generating huge amounts of IL-33 in the presence of TNF-α stimulation in vitro. Additionally, in vivo data demonstrated that administration of IL-33 increased the severity of experimental arthritis (3). Surprisingly, in the present study, serum IL-33 levels had no significant changes compared to the control group. Also there were no significant alterations in serum IL-33 levels in patients with DM and PM three months after treatment compared to the patients before treatment. In addition, serum IL-33 levels had no correlation with other clinical parameters inpatients with DM and PM. (3)

 

St2 role 

The reason for this may be that elevated levels of ST2 can bind to IL-33 and decrease the serum levels of IL-33 in patients with DM and PM. Dermatomyositis and Polymyositis are rare diseases, therefore, the number of subjects was not large enough to explore the relationship of cytokine levels and other serum parameters such as CK and CRP. 

In conclusion, high serum levels of IL-33 provide further evidence for activation of inflammatory and immune response in patients with DM/PM. This suggested that IL-33 may have a pathological function in DM/PM and will be a valuable marker for diagnosis of DM/PM, and anti-IL-33 may be a useful agent for the treatment of DM/PM, which should be considered by future investigations.(4)

 

Trials

In one trial, serum sST2 and IL-33 levels in 49 DM and 21 PM were detected by enzyme-linked immunosorbent assay (ELISA). Erythrocyte sedimentation rate (ESR), C-reactive protein (CRP), creatine kinase (CK), lactate dehydrogenase (LDH) and antinuclear antibody (ANA), anti-Jo-1 antibody and anti-Mi-2 antibody were tested by standard laboratory techniques. Interstitial lung disease (ILD) was identified on high-resolution computed tomography (HRCT). The visual analogue scale (VAS) of the disease activity, muscle strength, lung functional parameters and other clinical features of DM/PM patients were recorded as well.(4)

Sera sST2 levels were significantly higher in DM and PM patients and correlated with CRP, CK, LDH and VAS. The level of serum sST2 decreased after therapy. Conversely, serum levels of IL-33 in patients with PM and DM were not significantly higher than those from HC. (4) (5)
 

Relevance

The level of sST2 is elevated in sera of DM and PM patients. sST2 levels were correlated with other markers of disease activity. This data support that sST2 may play a role in DM and PM.

Footnotes : 

1.Hak AE, .Dermatomyositisand polymyositis: new treatment targets on the horizon.Neth J Med. 2011;69(10):410–21. [PubMed: 22058260]

2. Castro C,. Diagnosis and treatment of inflammatory

myopathy: issues and management. Ther Adv Musculoskelet

Dis. 2012;4(2):111–20. doi: 10.1177/1759720X11425092. [PubMed:

22870499]

3. Sugiura T.Increased IL-15 production of muscle cells in polymyositis

and dermatomyositis. Int Immunol. 2002;14(8):917–24.

[PubMed: 12147628]

4. Mielnik P,. Serum concentration of interleukin 15,

interleukin 2 receptor and TNF receptor in patients with polymyositis

and dermatomyositis: correlation to disease activity.

Rheumatol Int. 2012;32(3):639–43. doi: 10.1007/s00296-010-1692-y.

[PubMed: 21132303]

5.  Yuan l.  Serum levels of soluble ST2 and interleukin-33 in patients with dermatomyositis and polymyositis.Clinical and Experimental Rheumatology [2013, 31(3):428-432] . http://europepmc.org/abstract/med/23485578