Complementary organ expression of IL-1 vs. IL-6 and CSF-1 activities in normal and LPS-injected mice

Hacham, Moshe; Cristal, N; White, Rosalyn M.; Segal, Shraga; Apte, Ron N.

doi:10.1006/cyto.1995.0004

Cited by 28 publications

(13 citation statements)

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“…Systemic administration of endotoxin activates cells in many compartments, in terms of activation of NF-kB [36], production of cytokines [37,38], and expression of cytokine receptors [39]. Our ex vivo analysis confirms these observations for bronchoalveolar cells, peritoneal cells, and splenocytes and suggests that bone marrow cells do not contribute significantly to the production of TNF.…”

Section: Discussionsupporting

confidence: 78%

Compartmentalization of Tolerance to Endotoxin

2004

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Section: Discussionsupporting

confidence: 78%

Compartmentalization of Tolerance to Endotoxin

2004

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“…Importantly, IL-1α is only rarely secreted by living cells and in most cases is undetectable in body fluids. Previously, we demonstrated that in vivo , in steady-state homeostasis and in inflammation, IL-1α and IL-1β are differentially expressed in tissues, possibly pointing to their different physiological roles (32, 43). …”

Section: Similarities and Differences Between Il-1α And Il-1βmentioning

confidence: 99%

Unique versus redundant functions of IL-1α and IL-1β in the tumor microenvironment

Voronov¹

2013

Front. Immunol.

113

118

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Interleukin-1 (IL-1) is a major “alarm” upstream pro-inflammatory cytokine that also affects immunity and hematopoiesis by inducing cytokine cascades. In the tumor arena, IL-1 is produced by malignant or microenvironmental cells. As a pleiotropic cytokine, IL-1 is involved in tumorigenesis and tumor invasiveness but also in the control of anti-tumor immunity. IL-1α and IL-1β are the major agonists of IL-1, while IL-1Ra is a physiological inhibitor of pre-formed IL-1. In their secreted form, IL-1α and IL-1β bind to the same receptors and induce the same biological functions, but IL-1α and IL-1β differ in their compartmentalization within the producing cell or the microenvironment. IL-1β is only active in its processed, secreted form, and mediates inflammation, which promotes carcinogenesis, tumor invasiveness, and immunosuppression, whereas IL-1α is mainly cell-associated and in the tumor context, when expressed on the cell membrane, it stimulates anti-tumor cell immunity manifested by tumor regression. In the tumor milieu, extracellular levels of IL-1α are usually low and do not stimulate broad inflammation that promotes progression. Immunosuppression induced by IL-1β in the tumor microenvironment, mainly through MDSC induction, usually inhibits or masks anti-tumor cell immunity induced by cell-associated IL-1α. However, in different tumor systems, redundant or unique patterns of IL-1α and IL-1β expression and function have been observed. Recent breakthroughs in inflammasome biology and IL-1β processing/secretion have spurred the development of novel anti-IL-1 agents, which are being used in clinical trials in patients with diverse inflammatory diseases. Better understanding of the integrative role of IL-1α and IL-1β in distinct malignancies will facilitate the application of novel IL-1 modulation approaches at the bedside, in cancer patients with minimal residual disease (MRD), as an adjunct to conventional approaches to reduce the tumor burden.

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“…Importantly, IL-1a is only rarely secreted by living cells and in most cases is undetectable in body fluids. Previously, we demonstrated that in vivo, in steady-state homeostasis and in inflammation, IL-1a and IL-1b are differentially expressed in tissues, possibly pointing to their different physiological roles (Hacham et al 1996(Hacham et al , 2002.…”

Section: Similarities and Differences Of Il-1a And Il-1bmentioning

confidence: 94%

Pleiotropic and Differential Functions of IL-1α and IL-1β Shape the Tumor Microenvironment and Affect the Outcome of Malignancies

Apte

Voronov

2013

The Tumor Immunoenvironment

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Interleukin-1 (IL-1) is a major ''alarm'' upstream pro-inflammatory cytokine that also affects immunity and hemopoiesis by inducing cytokine cascades. In the tumor arena, IL-1 is produced by malignant or microenvironmental cells. As a pleiotropic cytokine, IL-1 is involved in tumorigenesis and tumor invasiveness and also in the activation of anti-tumor immunity. IL-1a and IL-1b are the major agonists of IL-1, while IL-1Ra is a physiological inhibitor of preformed IL-1. In their secreted form, IL-1a and IL-1b bind to the same receptors and induce the same biological functions. However, IL-1a and IL-1b differ in their compartmentalization within the producing cell or the microenvironment. IL-1b is only active in its secreted form and mediates inflammation, which promotes carcinogenesis, tumor invasiveness and immunosuppression. On the other hand, IL1a is mainly cell-associated; in the context of tumors, host-and tumor cell-derived IL-1a stimulates anti-tumor immunity, rather than inflammation. Recent breakthroughs in inflammasome biology and IL-1b processing/secretion have spurred the development of novel anti-IL-1 agents which are being used in clinical trials in patients with diverse diseases with inflammatory manifestations. Better understanding of the integrative role of IL-1a and IL-1b in the malignant process will enable the application of novel IL-1 modulation approaches at the bedside, in cancer patients with minimal residual disease (MRD), as an adjunct to conventional approaches to reduce the tumor burden.

show abstract

Complementary organ expression of IL-1 vs. IL-6 and CSF-1 activities in normal and LPS-injected mice

Cited by 28 publications

References 0 publications

Compartmentalization of Tolerance to Endotoxin

Compartmentalization of Tolerance to Endotoxin

Unique versus redundant functions of IL-1α and IL-1β in the tumor microenvironment

Pleiotropic and Differential Functions of IL-1α and IL-1β Shape the Tumor Microenvironment and Affect the Outcome of Malignancies

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