Time Course of Immune Response and Immunomodulation During Normal and Delayed Healing of Musculoskeletal Wounds

Muire, Preeti J.; Mangum, Lauren H.; Wenke, Joseph C.

doi:10.3389/fimmu.2020.01056

Cited by 78 publications

(82 citation statements)

References 203 publications

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“…23,24 Understanding the function of complex cytokine networks in pathogenesis requires comparison of expression profiles of multiple cytokines in health and disease states. 25 Cytokines can serve as molecular biomarkers that provide insight into the development, progression, and prognosis of both acute health threats such as sepsis 26 and trauma, 27 and of chronic disorders including, for example, autoimmune, 28 cardiopulmonary, 29,30 and neoplastic diseases. 5 Glioblastoma and brain metastases are particularly lethal neoplastic disorders with limited treatment options, 1,2 whose pathogenesis may be modulated by multiple cytokines.…”

Section: Discussionmentioning

confidence: 99%

Cytokine Profiling in Plasma from Patients with Brain Tumors Versus Healthy Individuals using 2 Different Multiplex Immunoassay Platforms

et al. 2021

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We compared the performance of two 96-well multiplex immunoassay platforms in assessing plasma cytokine concentrations in patients with glioblastoma (GBM; n = 27), individuals with melanoma, breast or lung cancer metastases to the brain (n = 17), and healthy volunteers (n = 11). Assays included a bead-based fluorescence MILLIPLEX® assay/Luminex (LMX) platform and 4 planar electrochemiluminescence kits from Meso Scale Discovery (MSD). The LMX kit evaluated 21 cytokines and the 3 MSD kits evaluated 20 cytokines in total, with 19 overlapping human cytokines between platforms (GM-CSF, IFNγ, IL-1β, IL-2, IL-4, IL-5, IL-6, IL-7, IL-8, IL-10, IL-12p70, IL-13, IL-17A, IL-21, IL-23, MIP-1α, MIP-1β, MIP-3α, TNFα). The MSD platform had lower LLoQs (lower limits of quantification) than LMX for 17/19 cytokines, and higher LLoQs for IFN-γ and IL-21. The ULoQs were higher in LMX versus MSD assays for 17/19 shared analytes, but lower than MSD for IL-17A and IL-21. With LMX, all 19 shared analytes were quantifiable in each of 55 samples. Although MSD recombinant protein standard curves indicated lower LLoQs than LMX for most cytokines, MSD detected 7/19 (37%) native analytes in <75% of samples, including 0% detection for IL-21 and 8% for IL-23. The LMX platform categorized identical samples at greater concentrations than the MSD system for most analytes (MIP-1β the sole exception), sometimes by orders of magnitude. This mismatched quantification paradigm was supported by Bland-Altman analysis. LMX identified significantly elevated levels of 10 of 19 circulating cytokines in GBM: GM-CSF, IFN-γ, IL-1β, IL-5, IL-10, IL-17A, IL-21, IL-23, MIP-1α, and MIP-3α, consistent with prior findings and confirming the utility of applying appropriate multiplex immunoassay technologies toward developing a cytokine signature profile for GBM.

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Section: Discussionmentioning

confidence: 99%

Cytokine Profiling in Plasma from Patients with Brain Tumors Versus Healthy Individuals using 2 Different Multiplex Immunoassay Platforms

et al. 2021

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“…These reparative macrophages found later during the repair process enhance the differentiation and fusion of myoblasts to form myotubes that later fuse to reseal damaged myofibres, mainly through secretion of anti-inflammatory factors, such as TGF-β1 [ 15 , 92 ]. A similar process occurs during bone fracture healing, with similar temporal macrophage cross-talk occurring with osteoblasts/osteoclasts rather than myocytes (reviewed by [ 96 ]. It is well known that musculoskeletal repair is delayed in elderly humans and mice and this is strongly associated with an altered inflammatory responses as shown by a cross-transplantation study of muscle grafts between young (3 months) and very old (27–29 months) C57BL/6J female mice [ 97 ].…”

Section: Background: Macrophage Function and Healthy Ageingmentioning

confidence: 99%

Macrophage function in the elderly and impact on injury repair and cancer

et al. 2021

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Older age is associated with deteriorating health, including escalating risk of diseases such as cancer, and a diminished ability to repair following injury. This rise in age-related diseases/co-morbidities is associated with changes to immune function, including in myeloid cells, and is related to immunosenescence. Immunosenescence reflects age-related changes associated with immune dysfunction and is accompanied by low-grade chronic inflammation or inflammageing. This is characterised by increased levels of circulating pro-inflammatory cytokines such as tumor necrosis factor (TNF), interleukin (IL)-1β and IL-6. However, in healthy ageing, there is a concomitant age-related escalation in anti-inflammatory cytokines such as transforming growth factor-β1 (TGF-β1) and IL-10, which may overcompensate to regulate the pro-inflammatory state. Key inflammatory cells, macrophages, play a role in cancer development and injury repair in young hosts, and we propose that their role in ageing in these scenarios may be more profound. Imbalanced pro- and anti-inflammatory factors during ageing may also have a significant influence on macrophage function and further impact the severity of age-related diseases in which macrophages are known to play a key role. In this brief review we summarise studies describing changes to inflammatory function of macrophages (from various tissues and across sexes) during healthy ageing. We also describe age-related diseases/co-morbidities where macrophages are known to play a key role, focussed on injury repair processes and cancer, plus comment briefly on strategies to correct for these age-related changes.

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“…Although, when shifted to type 1/Th1 immune responses it has a damaging aspect, these same signals are crucial for muscle regeneration, and development. However, if the type 1 response (which includes M1 macrophages and Th1 cells) is not resolved, muscle differentiation does not take place and fibrosis is established (Zhang et al, 2014;Tidball, 2017;Muire et al, 2020).…”

Section: Immune Cross Talk In Skeletal Muscle: the Role Of Treg Cellsmentioning

confidence: 99%

Crosstalk Between Innate and T Cell Adaptive Immunity With(in) the Muscle

et al. 2020

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Growing evidence demonstrates a continuous interaction between the immune system and the skeletal muscle in inflammatory diseases of different pathogenetic origins, in dystrophic conditions such as Duchenne Muscular Dystrophy as well as during normal muscle regeneration. Although one component of the innate immunity, the macrophage, has been extensively studied both in disease conditions and during cell or gene therapy strategies aiming at restoring muscular functions, much less is known about dendritic cells and their primary immunological targets, the T lymphocytes. This review will focus on the dendritic cells and T lymphocytes (including effector and regulatory T-cells), emphasizing the potential cross talk between these cell types and their influence on the structure and function of skeletal muscle.

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Time Course of Immune Response and Immunomodulation During Normal and Delayed Healing of Musculoskeletal Wounds

Cited by 78 publications

References 203 publications

Cytokine Profiling in Plasma from Patients with Brain Tumors Versus Healthy Individuals using 2 Different Multiplex Immunoassay Platforms

Cytokine Profiling in Plasma from Patients with Brain Tumors Versus Healthy Individuals using 2 Different Multiplex Immunoassay Platforms

Macrophage function in the elderly and impact on injury repair and cancer

Crosstalk Between Innate and T Cell Adaptive Immunity With(in) the Muscle

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