Inducible production of interleukin-6 by human polymorphonuclear neutrophils: role of granulocyte-macrophage colony-stimulating factor and tumor necrosis factor-alpha

Cicco, N. A.; Lindemann, A.; Vandenbussche, Pierre-Yves; Lübbert, Michael; Gauss, Jutta; Mertelsmann, Roland; Herrmann, F

doi:10.1182/blood.v75.10.2049.2049

Cited by 173 publications

(53 citation statements)

References 24 publications

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“…As can be seen in Figure 4, this coincided with an increase in IL-6 mRNA, as measured by in situ hybridization, within skeletal muscle fibers comparing PRE with POST contraction. At PRE, IL-6 mRNA was expressed peripherally at low levels around all fibers, and there was a virtual absence of IL-6 in the center of the myocytes, suggesting that, at rest, IL-6 in skeletal muscle tissue is likely to be located in cell types other than myocytes (7). However, at POST, IL-6 mRNA was selectively expressed throughout some, but not all, muscle fibers ( Fig.…”

Section: Il-6 Mrna Is Elevated After Exercise In Skeletal Muscle Fibersmentioning

confidence: 92%

Skeletal myocytes are a source of interleukin‐6 mRNA expression and protein release during contraction: evidence of fiber type specificity

Hiscock¹,

Chan²,

et al. 2004

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In this study, we aimed to determine whether skeletal muscle cells per se are a source of interleukin (IL)-6 during contraction and whether IL-6 production is fiber type specific. Muscle biopsy samples were collected from seven males before (PRE) and after (POST) completing 120 min of continuous bicycle ergometry. Biopsies were sectioned and analyzed for the following: IL-6 protein detected by immunohistochemistry (IHC), IL-6 mRNA content detected by in situ hybridization, fiber type measured by either IHC or myofibrillar ATPase activity stain, and glycogen content measured by periodic acid schiff (PAS) assay. Fibers were qualitatively categorized according to glycogen content to one of five groups (1-5), with 1 being very low (LOW) and 5 being very high (HIGH) glycogen. Total fluorescence (PRE vs. POST) and glycogen-dependent fluorescence (LOW vs. HIGH) of IL-6 protein were quantitated using Metamorph software. Total IL-6 protein was elevated from PRE to POST exercise (P<0.05). At PRE, IL-6 protein was evenly distributed across all fibers at low levels, consistent with glycogen distribution. At POST, IL-6 protein was greater (P<0.05) in HIGH compared with LOW glycogen fibers, which coincided with type 2 fibers. IL-6 mRNA was distributed peripherally in all fibers at PRE. At POST, however, IL-6 mRNA appeared predominantly in type 2 fibers, which also had higher glycogen content (P<0.05). These data demonstrate that myocytes per se are a source of IL-6 produced during contraction. Our data also suggest that type 2 fibers predominantly produce IL-6 during muscle contractile activity.

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Section: Il-6 Mrna Is Elevated After Exercise In Skeletal Muscle Fibersmentioning

confidence: 92%

Skeletal myocytes are a source of interleukin‐6 mRNA expression and protein release during contraction: evidence of fiber type specificity

Hiscock¹,

Chan²,

et al. 2004

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“…8 Secretion of IL-6 has been measured after some of the used stimuli. 6,9 Furthermore, TNF-a mRNA has been demonstrated in stimulated PMN, 10 but the measured cytokine secretion 10,11 could not be confirmed by other authors. 9 Most interesting are the results concerning IL-8, a potent stimulator of PMN.…”

Section: Introductionmentioning

confidence: 88%

“…For IL-1b, mRNA has been found in stimulated PMN 3,4 as well as cytokine production in their supernatants. 4,5 Messenger RNA for IL-6 has been obtained after stimulation of PMN 6 and even constitutively, 7 but there are also reports that it could not be detected at all. 8 Secretion of IL-6 has been measured after some of the used stimuli.…”

Section: Introductionmentioning

confidence: 99%

Cytokine production of neutrophils is limited to interleukin‐8

1996

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Since granulocytes are one of the first cell types at sites of inflammation, investigation of their capacity to produce cytokines has concentrated on interleukin-1 beta (IL-1 beta), IL-6, IL-8 and tumour necrosis factor-alpha (TNF-alpha). However, the results are subject to controversy. Incapability to produce cytokines as well as a broad panel of cytokines induced by isolation procedures are reported. The purpose of this study was to investigate the capacity of non-prestimulated neutrophils to produce the above-mentioned cytokines in response to stimulation with lipopolysaccharide or zymosan. In reverse transcription-polymerase chain reactions, we found IL-8 mRNA directly after isolation in unstimulated cells, whereas mRNA for IL-1 beta, IL-6 and TNF-alpha only appeared after stimulation. By means of flow cytometry we ruled out the possibility of prestimulation of the neutrophils during isolation, proving that IL-8 mRNA is produced constitutively by neutrophils. In enzyme-linked immunosorbent assays we found that, compared with controls, only IL-8 was released at significantly higher levels after 24 hr of stimulation, giving a further indication that neutrophils have an immunoregulatory influence driven by IL-8. We can confirm neither a constitutive nor a post-stimulatory release of IL-1 beta, IL-6, or TNF-alpha by neutrophils, as had been reported by others. These observations may be due to prestimulation, handling and culturing of the granulocytes, or to monocyte contamination. Collectively, our results show that granulocytes have a preformed capacity to produce the cytokine IL-8 and that the production of proinflammatory cytokines by neutrophils is limited to IL-8.

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“…Previous work [26][27][28][29][30][31] has shown that neutrophils can express IL-1/3 when exposed to certain pro-inflammatory stimuli. Levels of IL-1/3 mRNA were undetectable in freshly-isolated blood neutrophils ( Fig.…”

Section: Interleukin-l T~ Expressionmentioning

confidence: 99%

“…Furthermore, exposure of blood neutrophils to low concentrations of the chemotactic peptide fMet-Leu-Phe [22] or the cytokines y-interferon [23], GM-CSF [24] and G-CSF [25] results in a rapid and selective increase in gene expression. This up-regulated gene expression greatly enhances the survival of functional neutrophils and also results in the expression of several secondary cytokines such as IL-1/3, G-CSF, GM-CSF, TNF-a, a-interferon, IL-6 and IL-8 [26][27][28][29][30][31][32][33]. It is not known, however, if neutrophils express such cytokines in vivo.…”

Section: Introductionmentioning

confidence: 99%

Cytokine expression by inflammatory neutrophils

Quayle

Adams

Bucknall

et al. 1994

FEMS Immunology &Amp; Medical Microbiology

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Bloodstream neutrophils do not express mRNA for interleukin-1 beta (IL-1 beta), but transcripts for this cytokine are rapidly induced following exposure to recombinant granulocyte-macrophage colony-stimulating factor (rGM-CSF) in vitro. Levels of IL-1 beta mRNA reach maximal values 1 h after exposure to rGM-CSF and then decline to near basal levels by 4 h. Similarly, rGM-CSF treatment of blood neutrophils in vitro induced increases in levels of mRNA for IL-6 and tumour necrosis factor-alpha (TNF-alpha). RNA extracted from neutrophils isolated from the synovial fluid of patients with rheumatoid arthritis expressed low, but significant levels of IL-1 beta mRNA that were between 0.5 and 3% of the levels that could be maximally induced by rGM-CSF treatment of blood neutrophils. However, transcripts for TNF-alpha and IL-6 were not detected in these synovial fluid neutrophils. mRNA for transforming growth factor-beta (TGF-beta) was constitutively expressed in blood and synovial fluid neutrophils and transcripts for this cytokine were not altered by rGM-CSF exposure. Because of the transient nature of IL-1 beta expression by activated neutrophils, we propose that the low levels of expression of mRNA for this cytokine in the synovial fluid neutrophils represents expression by a small, perhaps newly-recruited and activated, sub-population of cells. IL-1 beta expression by this sub-population may thus contribute to the pathogenesis of rheumatoid disease.

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Inducible production of interleukin-6 by human polymorphonuclear neutrophils: role of granulocyte-macrophage colony-stimulating factor and tumor necrosis factor-alpha

Cited by 173 publications

References 24 publications

Skeletal myocytes are a source of interleukin‐6 mRNA expression and protein release during contraction: evidence of fiber type specificity

Skeletal myocytes are a source of interleukin‐6 mRNA expression and protein release during contraction: evidence of fiber type specificity

Cytokine production of neutrophils is limited to interleukin‐8

Cytokine expression by inflammatory neutrophils

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