Hip Osteonecrosis Is Associated with Increased Plasma IL-33 Level

Ma, Jinhui; Guo, Wanshou; Li, Zirong; Wang, Bailiang; Li, Shirui; Wang, Peng

doi:10.1155/2017/1732638

Cited by 15 publications

(13 citation statements)

References 34 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…In our study, the healthy volunteers ( n = 12) had an average baseline IL33 level of 22.8 pg/mL. This is midrange (5–53 pg/mL) for what has been reported in healthy adult humans [39–43]. In injured patients, IL33 levels were the highest in the first 4 hours after presentation, and this was followed by persistent elevations through 7 days in patients that remained in the ICU.…”

Section: Resultssupporting

confidence: 60%

IL33-mediated ILC2 activation and neutrophil IL5 production in the lung response after severe trauma: A reverse translation study from a human cohort to a mouse trauma model

Guardado

Hoffman

et al. 2017

PLoS Med

View full text Add to dashboard Cite

BackgroundThe immunosuppression and immune dysregulation that follows severe injury includes type 2 immune responses manifested by elevations in interleukin (IL) 4, IL5, and IL13 early after injury. We hypothesized that IL33, an alarmin released early after tissue injury and a known regulator of type 2 immunity, contributes to the early type 2 immune responses after systemic injury.Methods and findingsBlunt trauma patients admitted to the trauma intensive care unit of a level I trauma center were enrolled in an observational study that included frequent blood sampling. Dynamic changes in IL33 and soluble suppression of tumorigenicity 2 (sST2) levels were measured in the plasma and correlated with levels of the type 2 cytokines and nosocomial infection. Based on the observations in humans, mechanistic experiments were designed in a mouse model of resuscitated hemorrhagic shock and tissue trauma (HS/T). These experiments utilized wild-type C57BL/6 mice, IL33-/- mice, B6.C3(Cg)-Rorasg/sg mice deficient in group 2 innate lymphoid cells (ILC2), and C57BL/6 wild-type mice treated with anti-IL5 antibody.Severely injured human blunt trauma patients (n = 472, average injury severity score [ISS] = 20.2) exhibited elevations in plasma IL33 levels upon admission and over time that correlated positively with increases in IL4, IL5, and IL13 (P < 0.0001). sST2 levels also increased after injury but in a delayed manner compared with IL33. The increases in IL33 and sST2 were significantly greater in patients that developed nosocomial infection and organ dysfunction than similarly injured patients that did not (P < 0.05). Mechanistic studies were carried out in a mouse model of HS/T that recapitulated the early increase in IL33 and delayed increase in sST2 in the plasma (P < 0.005). These studies identified a pathway where IL33 induces ILC2 activation in the lung within hours of HS/T. ILC2 IL5 up-regulation induces further IL5 expression by CXCR2+ lung neutrophils, culminating in early lung injury. The major limitations of this study are the descriptive nature of the human study component and the impact of the potential differences between human and mouse immune responses to polytrauma. Also, the studies performed did not permit us to make conclusions about the impact of IL33 on pulmonary function.ConclusionsThese results suggest that IL33 may initiate early detrimental type 2 immune responses after trauma through ILC2 regulation of neutrophil IL5 production. This IL33–ILC2–IL5–neutrophil axis defines a novel regulatory role for ILC2 in acute lung injury that could be targeted in trauma patients prone to early lung dysfunction.

show abstract

Section: Resultssupporting

confidence: 60%

IL33-mediated ILC2 activation and neutrophil IL5 production in the lung response after severe trauma: A reverse translation study from a human cohort to a mouse trauma model

Guardado

Hoffman

et al. 2017

PLoS Med

View full text Add to dashboard Cite

show abstract

“…Interleukin‐33 (IL‐33), a member of the interleukin‐1 (IL‐1) family, acts as a proinflammatory cytokine via the cell‐surface receptor ST2 . IL‐33 acts on different types of cells, such as osteoblasts, osteoclasts, and osteocytes, and is involved in several acute and chronic inflammatory and autoimmune diseases, such as rheumatoid arthritis and hip osteonecrosis . IL‐33/ST2 signaling has been suggested to be an important bone‐protecting cytokine that decreases bone loss in the femur, with reduced osteoclast formation and activity and stimulation of osteoblastic function .…”

Section: Introductionmentioning

confidence: 99%

“…6 IL-33 acts on different types of cells, such as osteoblasts, osteoclasts, and osteocytes, [7][8][9] and is involved in several acute and chronic inflammatory and autoimmune diseases, 10 such as rheumatoid arthritis 11 and hip osteonecrosis. 12 IL-33/ST2 signaling has been suggested to be an important bone-protecting cytokine that decreases bone loss in the femur, with reduced osteoclast formation and activity 13 and stimulation of osteoblastic function. 9 IL-33 also increases antiosteoclastogenic cytokines, 14 which interfere with the production of receptor activator of nuclear factor κ B ligand (RANKL) and macrophage colony-stimulating factor, 8,9,13,14 thus acting in the bone via indirect pathways.…”

Section: Introductionmentioning

confidence: 99%

ST2 regulates bone loss in a site‐dependent and estrogen‐dependent manner

Macari

Madeira

Lima

et al. 2018

J of Cellular Biochemistry

View full text Add to dashboard Cite

Interleukin-33 (IL-33) and its receptor, ST2, are implicated in bone remodeling. The lack of estrogen after menopause results in an accelerated bone loss. Here we investigated the role of ST2 in the bone loss induced by estrogen deficiency. ST2-deficient mice (ST2 ) and their littermates (wildtype [WT]) were ovariectomized (OVX), while ovary-intact mice were used as controls. Bone sites were analyzed by microcomputed tomography, histomorphometry, and quantitative real-time polymerase chain reaction (qPCR). Deletion of IL-33 or ST2 resulted in a similar bone loss in the femur and maxilla. Ovariectomy in WT mice caused bone loss in the same areas. The lack of ST2 in OVX mice did not alter bone remodeling in the femur but prevented bone loss in the maxilla. Consistently, ovariectomy increased the IL-33 messenger RNA (mRNA) levels in the maxilla but not in the femur. Under mechanical stimulation, ovariectomy and ST2 deletion independently increased bone remodeling induced by orthodontic tooth movement, which was also associated with a greater number of osteoclasts and a reduced number of osteoblasts in the maxillary bone. ST2 OVX mice, however, displayed twice as many osteoblasts as that of WT OVX mice. Ovariectomy and ST2 deletion differently altered the cytokine mRNA levels in the maxilla. Remarkably, interleukin-10 expression was decreased in both WT OVX and ST2 mice, and this reduction was completely restored in ST2 OVX mice. The results demonstrate that estrogen and IL33/ST2 independently protect against bone loss. However, the ovariectomy-induced bone loss is IL-33/ST2-dependent in the maxilla but not in the femur, indicating a bimodal and site-specific role of ST2 in bone remodeling.

show abstract

“…At present, there are not many researches conducted in this branch. In our previous studies, we found that IL-33 was associated with the prognosis of patients with ONFH [17]. This gives us the inspiration to explore the role of immune cells and immunomodulatory cells in ONFH.…”

Section: Introductionmentioning

confidence: 89%

The Role of Immune Regulatory Cells in Nontraumatic Osteonecrosis of the Femoral Head: A Retrospective Clinical Study

Gao

et al. 2019

BioMed Research International

Self Cite

View full text Add to dashboard Cite

The immunologic factors have been implicated in the pathogenesis of osteonecrosis. We aimed to investigate the potential role of immune regulatory cells in the development of osteonecrosis of femoral head (ONFH). Sixty-seven patients diagnosed with ONFH and fifty-eight age-, height-, and weight-matched healthy subjects were included in this retrospective study between September 2015 and September 2018. The flow cytometry was used to test the count, percentage, and ratio of T and B lymphocyte subsets in peripheral blood. The T and B lymphocyte levels were compared among different ARCO stages, CJFH types, and etiology groups. The total lymphocyte count, CD3+T cells, Ts cells (CD3+CD8+), B-1 cell count, and B-1 cells (CD5+CD19+) were significantly higher in the patients with ONFH than those in the control subjects. The percentage of T lymphocytes in the patients with ARCO IV stage was significantly smaller than that in the ONFH patients with ARCO II and III stages. The percentage of inhibitory T lymphocytes in patients with CJFH type L3 was significantly smaller than that in the patients with types L1 and L2. In terms of the different ONFH etiologies, the total lymphocyte count and Ts cells (CD3+CD8+) were significantly lower in the ONFH patients induced by excessive alcohol intake than those in the idiopathic ONFH patients. Our results seem to indicate that immune regulatory cells, such as T and B lymphocytes, play an important role in the pathogenesis of ONFH. The development and progression of ONFH may be associated with immune system imbalance.

show abstract

Hip Osteonecrosis Is Associated with Increased Plasma IL-33 Level

Cited by 15 publications

References 34 publications

IL33-mediated ILC2 activation and neutrophil IL5 production in the lung response after severe trauma: A reverse translation study from a human cohort to a mouse trauma model

IL33-mediated ILC2 activation and neutrophil IL5 production in the lung response after severe trauma: A reverse translation study from a human cohort to a mouse trauma model

ST2 regulates bone loss in a site‐dependent and estrogen‐dependent manner

The Role of Immune Regulatory Cells in Nontraumatic Osteonecrosis of the Femoral Head: A Retrospective Clinical Study

Contact Info

Product

Resources

About