ReviewNew insights into chronic inflammation-induced immunosuppression
Section snippets
Chronic inflammation and induced immunosuppression
An inflammatory process reflects the host's principal immune response aimed at eliminating foreign substances invading the body, or abnormally generated self-compounds produced during tissue injury. The response promotes the optimal restoration of tissue structure and function, but must also rapidly turned off in order to prevent over reaction that could result in irreversible damage [1], [2], [3]. In general, the innate immune response is initiated within minutes, and if necessary, it is
Clinical implications utilizing chronic immunosuppression for therapy
There is no doubt that chronic inflammation-induced immunosuppression drives serious complications and consequences in associated pathologies. However, there is another side of the coin in which the suppression of autoreactive cells and neutralization of the over-activated immune response could serve clinical goals, and even represent the only way to enable recovery. The suppressive function of MDSCs is the normal outcome of exacerbated inflammatory response [46]. These cells serve as key
Clinical implications in targeting immunosuppression
In most cases of chronic inflammation, the resulting milieu is deleterious to the host due to the array of pro-inflammatory cells and soluble factors that lead to immunosuppression, alongside susceptibility to cancer, opportunistic infections and the limited success of immune-based therapies. As opposed to the pathologies described in the previous section where inducing an immunosuppressive environment is suggested as a therapeutic strategy to inhibit autoimmune diseases or transplant
Biomarkers
Patients suffering from diseases characterized by chronic inflammation including autoimmune disorders, infections and cancer, tend to develop complications due to the sustained inflammation and associated immunosuppression, and in many cases, are subjected to a variety of treatments and drugs that differ in their impact on the immune system.
Currently, diagnostic tests that can distinguish between acute and chronic inflammation, and the ensuing immunosuppression are not available in the clinic,
Concluding remarks
The execution of an acute inflammatory response is critical to protect the body against tissue injury and pathogens, and is supported by structural and functional restoration processes, while unresolved chronic inflammation has harmful effects on the host's systems. In this review, we discussed the ramifications of chronic inflammatory responses shared by different types of chronic pathologies, predisposing the individuals to a developing immunosuppressive environment and accompanying disease
Conflict of interest statement
The authors, Julia Kanterman, Moshe Sade-Feldman and Michal Baniyash, submitting this manuscript declare that there are no conflicts of interest.
Acknowledgements
We gratefully acknowledge the support of the Society of Research Associates of the Lautenberg Center, the Concern Foundation of Los Angeles and the Harold B. Abramson Chair in Immunology. This study was supported by the US-Israel Binational Science Foundation, The Israel Academy of Sciences and Humanities, The Israeli Ministry of Health, The Israel Cancer Research Foundation (ICRF), The Joint German-Israeli Research Program (DKFZ), and by The Joseph and Matilda Melnick Funds.
References (149)
Chronic inflammation, immunosuppression and cancer: new insights and outlook
Semin Cancer Biol
(2006)- et al.
A common pathway mediated through Toll-like receptors leads to T- and natural killer-cell immunosuppression
Blood
(2008) - et al.
Macrophages, innate immunity and cancer: balance, tolerance, and diversity
Curr Opin Immunol
(2010) Toll-like receptors, inflammation and cancer
Semin Cancer Biol
(2006)- et al.
Anti-TNF therapy: safety aspects of taking the risk
Autoimmun Rev
(2011) - et al.
Role of TNF/TNFR in autoimmunity: specific TNF receptor blockade may be advantageous to anti-TNF treatments
Cytokine Growth Factor Rev
(2002) - et al.
Myeloid-derived suppressor cell role in tumor-related inflammation
Cancer Lett
(2008) - et al.
Reactive oxygen species and development in microbial eukaryotes
Trends Microbiol
(2005) Cyclooxygenase-2 in oncogenesis
Clin Chim Acta
(2011)- et al.
MicroRNAs in immune regulation—opportunities for cancer immunotherapy
Int J Biochem Cell Biol
(2010)
Targeting the stromal microenvironment in chronic inflammation
Curr Opin Pharmacol
Tumor-associated macrophages and the related myeloid-derived suppressor cells as a paradigm of the diversity of macrophage activation
Hum Immunol
Tuning microenvironments: induction of regulatory T cells by dendritic cells
Immunity
S100A8 and S100A9 in inflammation and cancer
Biochem Pharmacol
Foxp3-dependent microRNA155 confers competitive fitness to regulatory T cells by targeting SOCS1 protein
Immunity
Bone marrow myeloid-derived suppressor cells (MDSCs) inhibit graft-versus-host disease (GVHD) via an arginase-1-dependent mechanism that is up-regulated by interleukin-13
Blood
Inflammation and cancer: back to Virchow?
Lancet
The hallmarks of cancer
Cell
Hallmarks of cancer: the next generation
Cell
NF-kappaB activation in cancer: a challenge for ubiquitination- and proteasome-based therapeutic approach
Semin Cancer Biol
LPS induces CD40 gene expression through the activation of NF-kappaB and STAT-1alpha in macrophages and microglia
Blood
IKKbeta links inflammation and tumorigenesis in a mouse model of colitis-associated cancer
Cell
TGF-beta suppresses tumor progression in colon cancer by inhibition of IL-6 trans-signaling
Immunity
Overexpression of interleukin-1beta induces gastric inflammation and cancer and mobilizes myeloid-derived suppressor cells in mice
Cancer Cell
Chronic inflammation: a failure of resolution
Int J Exp Pathol
Molecular cues guiding inflammatory responses
Cardiovasc Res
Controlling the resolution of acute inflammation: a new genus of dual anti-inflammatory and proresolving mediators
J Periodontol
Chronic inflammation, the tumor microenvironment and carcinogenesis
Cell Cycle
TCR zeta-chain downregulation: curtailing an excessive inflammatory immune response
Nat Rev Immunol
Alterations in the expression of signal-transducing CD3 zeta chain in T cells from patients with chronic inflammatory/autoimmune diseases
Arch Immunol Ther Exp (Warsz)
NKG2D initiates caspase-mediated CD3zeta degradation and lymphocyte receptor impairments associated with human cancer and autoimmune disease
J Immunol
Sustained exposure to bacterial antigen induces interferon-gamma-dependent T cell receptor zeta down-regulation and impaired T cell function
Nat Immunol
Chronic inflammation promotes myeloid-derived suppressor cell activation blocking antitumor immunity in transgenic mouse melanoma model
Proc Natl Acad Sci USA
Macrophage heterogeneity and acute inflammation
Eur J Immunol
Why does inflammation persist: a dominant role for the stromal microenvironment
Expert Rev Mol Med
Monocyte recruitment during infection and inflammation
Nat Rev Immunol
NF-kappaB and STAT3 – key players in liver inflammation and cancer
Cell Res
Inflammation and cancer: interweaving microRNA, free radical, cytokine and p53 pathways
Carcinogenesis
Inflammation and liver cancer: new molecular links
Ann N Y Acad Sci
Chronic inflammation and oxidative stress in the genesis and perpetuation of cancer: role of lipid peroxidation, DNA damage, and repair
Langenbecks Arch Surg
Modulation of inflammatory signaling pathways by phytochemicals in ovarian cancer
Genes Nutr
Overcoming immunosuppression in the melanoma microenvironment induced by chronic inflammation
Cancer Immunol Immunother
Tumour necrosis factor and cancer
Nat Rev Cancer
Interleukin-6 trans-signalling in chronic inflammation and cancer
Scand J Immunol
Principles of interleukin (IL)-6-type cytokine signalling and its regulation
Biochem J
The role of iNOS-mediated DNA damage in infection- and asbestos-induced carcinogenesis
Ann N Y Acad Sci
Cyclooxygenase-2 expression and role of vasoconstrictor prostanoids in small mesenteric arteries from patients with Crohn's disease
Circulation
Cyclooxygenase-2 and gastric cancer
Cancer Metastasis Rev
MicroRNAs: new regulators of immune cell development and function
Nat Immunol
Role of miRNA-146a in the regulation of the innate immune response and cancer
Biochem Soc Trans
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2022, Seminars in Cancer BiologySystemic inflammation during the first year of life is associated with brain functional connectivity and future cognitive outcomes
2022, Developmental Cognitive NeuroscienceCitation Excerpt :Chronic inflammation, by contrast, is an inflammatory response that fails to resolve and may be detrimental to the host. Chronic inflammation is characterized by persistent elevation in systemic plasma concentrations of several cytokines, including C-reactive protein (CRP), and may contribute to immunosuppression, oxidative stress, and cytotoxicity (Raiten et al., 2015; Kanterman et al., 2012). Chronic inflammation may be caused by a variety of early adversities including recurrent infection, environmental exposures, and psychosocial stressors, with negative long-term health consequences (Danese et al., 2009; Shonkoff et al., 2012; Slopen et al., 2013).
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2021, Neurochemistry InternationalCitation Excerpt :Evidently, the disruption of BBB has an important role in maintaining the persistent neuroinflammation in the pathogenesis of AD (Zlokovic, 2011). It is known that chronic low-grade inflammation induces the counteracting anti-inflammatory/immunosuppressive response, i.e., the recruitment of myeloid-derived suppressor cells (MDSC) and regulatory T cells (Treg) as well as the polarization of macrophages/microglia into anti-inflammatory M2 phenotypes (Kanterman et al., 2012; Stubbe et al., 2013; Cherry et al., 2014; Salminen, 2020). This kind of immunosuppressive response seems to be present also in the inflamed brains of AD patients (Salminen et al., 2018; Salminen, 2021).
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These authors equally contributed to this work.