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Blockade of IL-36 receptor signaling does not prevent from TNF-induced arthritis.

Derer A, Groetsch B, Harre U, Böhm C, Towne J, Schett G, Frey S, Hueber AJ - PLoS ONE (2014)

Bottom Line: Furthermore, blockade of IL-36 signaling did not change histological signs of TNF-induced arthritis.Additionally, no alteration on bone homeostasis was observed in ex vivo murine and human osteoclast differentiation assays.Thus we conclude that IL-36α does not affect the development of inflammatory arthritis.

View Article: PubMed Central - PubMed

Affiliation: Department of Internal Medicine 3 and Institute for Clinical Immunology, University Hospital Erlangen, Erlangen, Germany; Department of Radiation Oncology, University Hospital Erlangen, Erlangen, Germany.

ABSTRACT

Introduction: Interleukin (IL)-36α is a newly described member of the IL-1 cytokine family with a known inflammatory and pathogenic function in psoriasis. Recently, we could demonstrate that the receptor (IL-36R), its ligand IL-36α and its antagonist IL-36Ra are expressed in synovial tissue of arthritis patients. Furthermore, IL-36α induces MAP-kinase and NFκB signaling in human synovial fibroblasts with subsequent expression and secretion of pro-inflammatory cytokines.

Methods: To understand the pathomechanism of IL-36 dependent inflammation, we investigated the biological impact of IL-36α signaling in the hTNFtg mouse. Also the impact on osteoclastogenesis by IL-36α was tested in murine and human osteoclast assays.

Results: Diseased mice showed an increased expression of IL-36R and IL-36α in inflamed knee joints compared to wildtype controls. However, preventively treating mice with an IL-36R blocking antibody led to no changes in clinical onset and pattern of disease. Furthermore, blockade of IL-36 signaling did not change histological signs of TNF-induced arthritis. Additionally, no alteration on bone homeostasis was observed in ex vivo murine and human osteoclast differentiation assays.

Conclusion: Thus we conclude that IL-36α does not affect the development of inflammatory arthritis.

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Related in: MedlinePlus

Unaltered clinical signs of arthritis in anti-IL36R treated hTNFtg mice.Clinical parameters: (A) body weight, (B) grip strength, (C) paw thickness and (D) joint thickness were regularly assessed in anti-IL36R treated hTNFtg mice between 4 and 8 weeks of age. Values represent the mean ±SEM (PBS control group n = 8; treatment group n = 9).
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pone-0101954-g002: Unaltered clinical signs of arthritis in anti-IL36R treated hTNFtg mice.Clinical parameters: (A) body weight, (B) grip strength, (C) paw thickness and (D) joint thickness were regularly assessed in anti-IL36R treated hTNFtg mice between 4 and 8 weeks of age. Values represent the mean ±SEM (PBS control group n = 8; treatment group n = 9).

Mentions: According to the enhanced expression of IL-36R and IL-36α in inflamed joints we hypothesized that IL-36R signaling blockade could ameliorate disease onset as well as severity. Therefore, we used an antibody against the IL-36 receptor that has been shown to actively suppress the psoriasis phenotype in IL-36tg [5]. Using anti-IL-36R antibody or PBS, hTNFtg mice were treated from 4 to 8 weeks of age, beginning at a time point where the clinical onset is not detectable yet. The assessment of clinical parameters revealed no significant differences in the development of weight of the treated mice compared to the control group (Figure 2A). In addition, the loss of grip strength appeared similar in both groups (Figure 2B). This clinical parameter was further confirmed by the measurement of metatarsal as well as ankle joint swelling (Figure 2C and D), whereby the course of the increase in thickness was analogous in the treatment- and the control-group. In conclusion, we did not observe differences in the severity of the disease course.


Blockade of IL-36 receptor signaling does not prevent from TNF-induced arthritis.

Derer A, Groetsch B, Harre U, Böhm C, Towne J, Schett G, Frey S, Hueber AJ - PLoS ONE (2014)

Unaltered clinical signs of arthritis in anti-IL36R treated hTNFtg mice.Clinical parameters: (A) body weight, (B) grip strength, (C) paw thickness and (D) joint thickness were regularly assessed in anti-IL36R treated hTNFtg mice between 4 and 8 weeks of age. Values represent the mean ±SEM (PBS control group n = 8; treatment group n = 9).
© Copyright Policy
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4128584&req=5

pone-0101954-g002: Unaltered clinical signs of arthritis in anti-IL36R treated hTNFtg mice.Clinical parameters: (A) body weight, (B) grip strength, (C) paw thickness and (D) joint thickness were regularly assessed in anti-IL36R treated hTNFtg mice between 4 and 8 weeks of age. Values represent the mean ±SEM (PBS control group n = 8; treatment group n = 9).
Mentions: According to the enhanced expression of IL-36R and IL-36α in inflamed joints we hypothesized that IL-36R signaling blockade could ameliorate disease onset as well as severity. Therefore, we used an antibody against the IL-36 receptor that has been shown to actively suppress the psoriasis phenotype in IL-36tg [5]. Using anti-IL-36R antibody or PBS, hTNFtg mice were treated from 4 to 8 weeks of age, beginning at a time point where the clinical onset is not detectable yet. The assessment of clinical parameters revealed no significant differences in the development of weight of the treated mice compared to the control group (Figure 2A). In addition, the loss of grip strength appeared similar in both groups (Figure 2B). This clinical parameter was further confirmed by the measurement of metatarsal as well as ankle joint swelling (Figure 2C and D), whereby the course of the increase in thickness was analogous in the treatment- and the control-group. In conclusion, we did not observe differences in the severity of the disease course.

Bottom Line: Furthermore, blockade of IL-36 signaling did not change histological signs of TNF-induced arthritis.Additionally, no alteration on bone homeostasis was observed in ex vivo murine and human osteoclast differentiation assays.Thus we conclude that IL-36α does not affect the development of inflammatory arthritis.

View Article: PubMed Central - PubMed

Affiliation: Department of Internal Medicine 3 and Institute for Clinical Immunology, University Hospital Erlangen, Erlangen, Germany; Department of Radiation Oncology, University Hospital Erlangen, Erlangen, Germany.

ABSTRACT

Introduction: Interleukin (IL)-36α is a newly described member of the IL-1 cytokine family with a known inflammatory and pathogenic function in psoriasis. Recently, we could demonstrate that the receptor (IL-36R), its ligand IL-36α and its antagonist IL-36Ra are expressed in synovial tissue of arthritis patients. Furthermore, IL-36α induces MAP-kinase and NFκB signaling in human synovial fibroblasts with subsequent expression and secretion of pro-inflammatory cytokines.

Methods: To understand the pathomechanism of IL-36 dependent inflammation, we investigated the biological impact of IL-36α signaling in the hTNFtg mouse. Also the impact on osteoclastogenesis by IL-36α was tested in murine and human osteoclast assays.

Results: Diseased mice showed an increased expression of IL-36R and IL-36α in inflamed knee joints compared to wildtype controls. However, preventively treating mice with an IL-36R blocking antibody led to no changes in clinical onset and pattern of disease. Furthermore, blockade of IL-36 signaling did not change histological signs of TNF-induced arthritis. Additionally, no alteration on bone homeostasis was observed in ex vivo murine and human osteoclast differentiation assays.

Conclusion: Thus we conclude that IL-36α does not affect the development of inflammatory arthritis.

Show MeSH
Related in: MedlinePlus