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Book ; Thesis: Interleukin-6

Jongh, Rafaël Frans José de

an important cytokine for the anesthesiologist?

2003

Author's details	door Rafa\200el Frans José De Jongh
Language	English ; Dutch
Size	VIII, 124 S. : graph. Darst.
Publishing country	Netherlands
Document type	Book ; Thesis
Thesis / German Habilitation thesis	Nijmegen, Univ., Diss., 2003
Note	Zsfassung in niederländ. Sprache
HBZ-ID	HT014098120
ISBN	90-9016653-X ; 978-90-9016653-7
Database	Catalogue ZB MED Medicine, Health

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Article ; Online: Pharmacological evaluation of rat dorsal root ganglion neurons as an in vitro model for diabetic neuropathy.

Peeraer, Eve / Van Lutsenborg, An / Verheyen, An / De Jongh, Raf / Nuydens, Rony / Meert, Theo F

Journal of pain research

2011 Volume 4, Page(s) 55–65

Abstract: Background: Diabetic neuropathy is a complication of diabetes mellitus that develops in about 50% of people with diabetes. Despite its widespread occurrence and devastating effects, this complication is still not fully understood, and there is no ... ...

Abstract	Background: Diabetic neuropathy is a complication of diabetes mellitus that develops in about 50% of people with diabetes. Despite its widespread occurrence and devastating effects, this complication is still not fully understood, and there is no treatment available to prevent its development. Methods: In this study, immunocytochemistry for activating transcription factor 3, a marker for cell injury, was used to investigate the stress response in dorsal root ganglion neurons in both in vitro and ex vivo models of diabetic neuropathy. Results: Our findings showed increased activating transcription factor 3 expression in hyperglycemic culture conditions and in dorsal root ganglion neurons isolated from diabetic rats. Glial cell line-derived neurotrophic factor, a substance with known neuroprotective properties, was able to reduce diabetes mellitus-induced neuronal stress in vitro, while gabapentin and carbamazepine, currently used to treat neuropathic pain, showed only limited effects. Conclusion: Growth factors may have a therapeutic benefit as neurotrophic agents in the treatment of diabetic peripheral neuropathy, but gabapentin and carbamazepine have no direct protective effect on sensory neurons. This research also indicates that immunocytochemistry for activating transcription factor 3 is a valuable tool for evaluation of pharmacological substances in dorsal root ganglion cultures.
Language	English
Publishing date	2011-02-14
Publishing country	New Zealand
Document type	Journal Article
ZDB-ID	2495284-9
ISSN	1178-7090 ; 1178-7090
ISSN (online)	1178-7090
ISSN	1178-7090
DOI	10.2147/JPR.S15452
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Article: Exogenous interleukin-6 increases cold allodynia in rats with a mononeuropathy.

Vissers, Kris C / De Jongh, Raf F / Hoffmann, Vincent L / Meert, Theo F

Cytokine

2005 Volume 30, Issue 4, Page(s) 154–159

Abstract: Interleukin-6 (IL-6) is a pleiotropic cytokine, signaling intracellularly via its unique membrane-bound receptor IL-6R and gp130. In peripheral nerve injury models, IL-6 and IL-6R are increased at the injured nerve and the respective dorsal root ganglion. ...

Abstract	Interleukin-6 (IL-6) is a pleiotropic cytokine, signaling intracellularly via its unique membrane-bound receptor IL-6R and gp130. In peripheral nerve injury models, IL-6 and IL-6R are increased at the injured nerve and the respective dorsal root ganglion. IL-6 is increased at the ipsilateral dorsal and ventral horn of the spinal cord. IL-6 is known to affect neuronal survival, differentiation and regeneration. It is involved in synaptic plasticity and hyperexitability and induces the synthesis or release of other substances with known neuroprotective or neuromodulatory effects. In this study, intrathecal administration of recombinant rat IL-6 to rats with a chronic constriction injury of the sciatic nerve, induced a logarithmic dose-dependent increase in cold allodynia with a threshold of 10 pg IL-6 and a maximal effect at 100 ng IL-6. Intrathecal administration of saline or denaturated IL-6 was without effect. In rats with a chronic constriction injury, systemic administered IL-6 did not induce a hyperalgesic effect, illustrating that IL-6 acts at the level of the dorsal root ganglion or the spinal cord. Intraplantar injection of 100 ng IL-6 in the operated hind paw resulted in an increased cold allodynia. This study demonstrates that the sensitivity to exogenous intrathecal or peripheral IL-6 increases in rats with a mononeuropathy.
MeSH term(s)	Animals ; Cold Temperature ; Interleukin-6/administration & dosage ; Male ; Mononeuropathies/physiopathology ; Pain/chemically induced ; Pain/physiopathology ; Rats ; Rats, Sprague-Dawley ; Sciatic Nerve/surgery
Chemical Substances	Interleukin-6
Language	English
Publishing date	2005-05-21
Publishing country	England
Document type	Journal Article
ZDB-ID	1018055-2
ISSN	1096-0023 ; 1043-4666
ISSN (online)	1096-0023
ISSN	1043-4666
DOI	10.1016/j.cyto.2005.01.008
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Article: Interleukin-6 and perioperative thermoregulation and HPA-axis activation.

De Jongh, Raf F / Vissers, Kris C / Booij, Leo H D J / De Jongh, Karen L / Vincken, Petra / Meert, Theo F

Cytokine

2003 Volume 21, Issue 5, Page(s) 248–256

Abstract: Surgery is followed by an acute-phase response, including hypothalamo-pituitary-adrenal (HPA)-axis activation and fever. Considering its physiological properties and its behaviour in plasma after stress and surgery, the pro-inflammatory cytokine ... ...

Abstract	Surgery is followed by an acute-phase response, including hypothalamo-pituitary-adrenal (HPA)-axis activation and fever. Considering its physiological properties and its behaviour in plasma after stress and surgery, the pro-inflammatory cytokine interleukin (IL)-6 is a putative candidate in eliciting these stress-related symptoms. However, evidence for this hypothesis is lacking. Rats subjected to individual psychological stress for 1h were injected intraperitoneally with saline or 3.33 microg per 100g rat neutralizing antibodies against rat IL-6. Thereafter, the single-housed rats were anaesthetized for 25 min, with or without undergoing a laparotomy. Intermittently, oesophageal temperatures were measured at defined time points. A parallel group of rats undergoing the same study protocol were decapitated, at time points when body temperatures differed, to obtain blood for measurement of plasma adrenocorticotropic hormone and corticosterone. Individual housing resulted in hyperthermia. Antibodies against IL-6 accelerated normalization of body temperature after individualizing stress, limited postoperative hyperthermia after laparotomy, but accentuated hyperthermia after anaesthesia alone. Antibody administration was not able to significantly influence the plasma hormone levels during any experiment. The present study indicates that IL-6 is a thermoregulatory factor during psychological, anaesthesiological and surgical stress, but the cytokine does not participate in HPA-axis activation until 6h after anaesthesia or surgery. A dose-finding study with antibodies against IL-6 ought to further identify the degree of contribution of IL-6 to perioperative thermoregulation.
MeSH term(s)	Adrenocorticotropic Hormone/blood ; Animals ; Body Temperature Regulation ; Body Weight ; Corticosterone/blood ; Hypothalamo-Hypophyseal System/metabolism ; Interleukin-6/antagonists & inhibitors ; Interleukin-6/metabolism ; Male ; Pituitary-Adrenal System/metabolism ; Rats ; Rats, Sprague-Dawley ; Stress, Physiological/blood ; Stress, Physiological/physiopathology
Chemical Substances	Interleukin-6 ; Adrenocorticotropic Hormone (9002-60-2) ; Corticosterone (W980KJ009P)
Language	English
Publishing date	2003-06-10
Publishing country	England
Document type	Journal Article
ZDB-ID	1018055-2
ISSN	1096-0023 ; 1043-4666
ISSN (online)	1096-0023
ISSN	1043-4666
DOI	10.1016/s1043-4666(03)00093-0
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Article: Adrenalectomy affects pain behavior of rats after formalin injection.

Vissers, Kris C / De Jongh, Raf F / Crul, Ben J P / Vinken, Petra / Meert, Theo F

Life sciences

2003 Volume 74, Issue 10, Page(s) 1243–1251

Abstract: Stressful stimuli can activate the hypothalamo-pituitary-adrenal-axis and the endogenous opioid system. In addition, corticosterone and opioid release might cause analgesia. This rat study used adrenalectomy for corticosterone withdrawal and naloxone ... ...

Abstract	Stressful stimuli can activate the hypothalamo-pituitary-adrenal-axis and the endogenous opioid system. In addition, corticosterone and opioid release might cause analgesia. This rat study used adrenalectomy for corticosterone withdrawal and naloxone administration for opioid antagonism in order to study pain behavior and hypophyseal hormone release in the plasma after a formalin test. Twelve days before the formalin testing, male Sprague Dawley rats underwent adrenalectomy or sham-adrenalectomy, and non-operated rats were used as reference. The number of flinches and the duration of licking or biting behavior were measured during the early and late phase. In reference and sham-operated rats, injection of formalin 5% resulted in a marked pain behavior in the early and late phase with significant increases in ACTH and corticosterone plasma levels. In adrenalectomized rats, pain behavior was decreased during both phases. Naloxone, administered before the late phase, did not alter pain behavior in sham or reference rats, whereas in adrenalectomized rats pain reactivity returned to those levels observed in reference rats. Beta-endorphin plasma levels above the detection limit were more frequently found in adrenalectomized rats. Thyrotropin and prolactin levels were not different between studied groups. We speculate that the observed reduced pain behavior in adrenalectomized rats after formalin, is the result of an increased production of pro-opiomelanocortin, the pro-drug of both adrenocorticotrophic hormone and beta-endorphin.
MeSH term(s)	Adrenalectomy ; Animals ; Behavior, Animal/drug effects ; Behavior, Animal/physiology ; Corticosterone/blood ; Formaldehyde ; Injections, Intraperitoneal ; Male ; Naloxone/pharmacology ; Narcotic Antagonists/pharmacology ; Pain/physiopathology ; Pain/psychology ; Pain Measurement ; Pituitary Hormones/blood ; Prolactin/pharmacology ; Rats ; Rats, Sprague-Dawley ; Thyrotropin/pharmacology ; beta-Endorphin/physiology
Chemical Substances	Narcotic Antagonists ; Pituitary Hormones ; Formaldehyde (1HG84L3525) ; Naloxone (36B82AMQ7N) ; beta-Endorphin (60617-12-1) ; Prolactin (9002-62-4) ; Thyrotropin (9002-71-5) ; Corticosterone (W980KJ009P)
Language	English
Publishing date	2003-10-17
Publishing country	Netherlands
Document type	Journal Article
ZDB-ID	3378-9
ISSN	1879-0631 ; 0024-3205
ISSN (online)	1879-0631
ISSN	0024-3205
DOI	10.1016/j.lfs.2003.07.040
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Article: The role of interleukin-6 in nociception and pain.

De Jongh, Raf F / Vissers, Kris C / Meert, Theo F / Booij, Leo H D J / De Deyne, Catharina S / Heylen, René J

Anesthesia and analgesia

2001 Volume 96, Issue 4, Page(s) 1096–1103

Abstract: Implications: That IL-6 is an interesting target in the study of pain is underscored by its biomolecular properties, its localization after experimental pain, and its modulating effect on pain after administration. ...

Abstract	Implications: That IL-6 is an interesting target in the study of pain is underscored by its biomolecular properties, its localization after experimental pain, and its modulating effect on pain after administration.
MeSH term(s)	Animals ; Humans ; Inflammation/metabolism ; Inflammation/physiopathology ; Inflammation Mediators/metabolism ; Inflammation Mediators/physiology ; Interleukin-6/metabolism ; Interleukin-6/physiology ; Neurons/drug effects ; Nociceptors/drug effects ; Nociceptors/physiology ; Pain/metabolism ; Pain/physiopathology
Chemical Substances	Inflammation Mediators ; Interleukin-6
Language	English
Publishing date	2001-06-08
Publishing country	United States
Document type	Journal Article ; Review
ZDB-ID	80032-6
ISSN	1526-7598 ; 0003-2999
ISSN (online)	1526-7598
ISSN	0003-2999
DOI	10.1213/01.ANE.0000055362.56604.78
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Article: The Fetomaternal Dependency of Cord Blood Interleukin-6

De Jongh, Raf F. / Puylaert, Martine / Bosmans, Eugene / Ombelet, Willem / Maes, Michael / Heylen, René

American Journal of Perinatology

1999 Volume 16, Issue 03, Page(s) 121–128

Abstract: Interleukin-6 (IL-6) plays a major role in hematopoiesis, immune functioning, and the acute phase response. In umbilical cord blood, this cytokine was thought to be a marker of neonatal defense to stress and infection, however, neonatal IL-6 production ... ...

Abstract	Interleukin-6 (IL-6) plays a major role in hematopoiesis, immune functioning, and the acute phase response. In umbilical cord blood, this cytokine was thought to be a marker of neonatal defense to stress and infection, however, neonatal IL-6 production is immature. We speculated that a maternal influence exists on neonatal IL-6, at least during uncomplicated deliveries. Of the 81 healthy parturients included in this study, 51 delivered vaginally, 20 with and 31 without epidural analgesia, and 30 underwent elective cesarean section, 20 with epidural and 10 with general anesthesia. Maternal blood was sampled on hospital admission and just after delivery. Neonatal blood was collected from the umbilical cord. A significant positive correlation was found between neonatal cord blood interleukin-6 levels and maternal serum IL-6 levels on admission (R = 0.57, P < 0.001) and just after delivery (R = 0.79, P < 0.001). This was not influenced by the type of delivery or anesthesia. Neonatal IL-6 levels were weakly negatively correlated with the duration of gestation and with the Apgar score 1 min after birth. A fetomaternal dependency of neonatal IL-6 on maternal serum IL-6 levels implies a priming or modulatory role of the maternal immune system on that of the neonate.
Keywords	Cytokine, interleukin-6 ; neonate ; fetomaternal dependency
Language	English
Publishing date	1999-01-01
Publishing place	Stuttgart ; New York
Document type	Article
ZDB-ID	605671-4
ISSN	1098-8785 ; 0735-1631
ISSN (online)	1098-8785
ISSN	0735-1631
DOI	10.1055/s-2007-993845
Database	Thieme publisher's database

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Article: Increased serum interleukin-8 and interleukin-10 in schizophrenic patients resistant to treatment with neuroleptics and the stimulatory effects of clozapine on serum leukemia inhibitory factor receptor.

Maes, Michael / Bocchio Chiavetto, Luisella / Bignotti, Stefano / Battisa Tura, Giani-Jean / Pioli, Rosaria / Boin, Francesco / Kenis, Gunter / Bosmans, Eugene / de Jongh, Raf / Altamura, Carlo A

Schizophrenia research

2002 Volume 54, Issue 3, Page(s) 281–291

Abstract: There is now evidence that schizophrenia may be accompanied by an activation of the monocytic and T-helper-2 (Th-2) arms of cell-mediated immunity (CMI) and by various alterations in the Th-1 arm of CMI. There is also evidence that repeated ... ...

Abstract	There is now evidence that schizophrenia may be accompanied by an activation of the monocytic and T-helper-2 (Th-2) arms of cell-mediated immunity (CMI) and by various alterations in the Th-1 arm of CMI. There is also evidence that repeated administration of typical and atypical antipsychotics may result in negative immunomodulatory effects. This study was carried out to examine (1) the serum concentrations of interleukin-8 (IL-8), IL-10, the soluble CD8 (sCD8) and the leukemia inhibitory factor receptor (LIF-R) in nonresponders to treatment with typical neuroleptics as compared with normal volunteers and responders to treatment; and (2) the effects of atypical antipsychotics on the above immune variables. The latter were determined in 17 nonresponders to treatment with neuroleptics and in seven normal volunteers and 14 schizophrenic patients who had a good response to treatment with antipsychotic agents. The nonresponders had repeated measurements of the immune variables before, and 2 and 4 months after treatment with clozapine or risperidone. Serum IL-8 and IL-10 were significantly higher in schizophrenic patients than in normal controls. The serum concentrations of the sCD8 were significantly increased 2 months, but not 4 months, after starting treatment with atypical antipsychotics. Serum LIF-R concentrations were significantly increased 2 and 4 months after starting treatment with atypical antipsychotics. It is concluded that: (1) schizophrenia is characterized by an activation of both pro-inflammatory and anti-inflammatory aspects of cell-mediated immunity; (2) prolonged treatment with atypical antipsychotics may increase the anti-inflammatory capacity of the serum in schizophrenic patients by increasing serum LIF-R concentrations; and (3) short-term treatment with clozapine may induce signs of immune activation which disappear upon prolonged treatment.
MeSH term(s)	Adult ; Analysis of Variance ; Antipsychotic Agents/immunology ; Antipsychotic Agents/pharmacology ; Case-Control Studies ; Clozapine/immunology ; Clozapine/pharmacology ; Drug Resistance/immunology ; Female ; Humans ; Interleukin-10/blood ; Interleukin-8/blood ; Leukemia Inhibitory Factor Receptor alpha Subunit ; Male ; Middle Aged ; Receptors, Cytokine/blood ; Receptors, Cytokine/drug effects ; Receptors, OSM-LIF ; Regression Analysis ; Schizophrenia/drug therapy ; Schizophrenia/immunology
Chemical Substances	Antipsychotic Agents ; Interleukin-8 ; LIFR protein, human ; Leukemia Inhibitory Factor Receptor alpha Subunit ; Receptors, Cytokine ; Receptors, OSM-LIF ; Interleukin-10 (130068-27-8) ; Clozapine (J60AR2IKIC)
Language	English
Publishing date	2002-01-28
Publishing country	Netherlands
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	639422-x
ISSN	1573-2509 ; 0920-9964
ISSN (online)	1573-2509
ISSN	0920-9964
DOI	10.1016/s0920-9964(00)00094-3
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Article ; Online: HIV protease inhibitors Nelfinavir and Lopinavir/Ritonavir markedly improve lung pathology in SARS-CoV-2-infected Syrian hamsters despite lack of an antiviral effect.

Foo, Caroline S / Abdelnabi, Rana / Kaptein, Suzanne J F / Zhang, Xin / Ter Horst, Sebastiaan / Mols, Raf / Delang, Leen / Rocha-Pereira, Joana / Coelmont, Lotte / Leyssen, Pieter / Dallmeier, Kai / Vergote, Valentijn / Heylen, Elisabeth / Vangeel, Laura / Chatterjee, Arnab K / Annaert, Pieter P / Augustijns, Patrick F / De Jonghe, Steven / Jochmans, Dirk /

Gouwy, Mieke / Cambier, Seppe / Vandooren, Jennifer / Proost, Paul / van Laer, Christine / Weynand, Birgit / Neyts, Johan

Antiviral research

2022 Volume 202, Page(s) 105311

Abstract: Nelfinavir is an HIV protease inhibitor that has been widely prescribed as a component of highly active antiretroviral therapy, and has been reported to exert in vitro antiviral activity against SARS-CoV-2. We here assessed the effect of Nelfinavir in a ... ...

Abstract	Nelfinavir is an HIV protease inhibitor that has been widely prescribed as a component of highly active antiretroviral therapy, and has been reported to exert in vitro antiviral activity against SARS-CoV-2. We here assessed the effect of Nelfinavir in a SARS-CoV-2 infection model in hamsters. Despite the fact that Nelfinavir, [50 mg/kg twice daily (BID) for four consecutive days], did not reduce viral RNA load and infectious virus titres in the lung of infected animals, treatment resulted in a substantial improvement of SARS-CoV-2-induced lung pathology. This was accompanied by a dense infiltration of neutrophils in the lung interstitium which was similarly observed in non-infected hamsters. Nelfinavir resulted also in a marked increase in activated neutrophils in the blood, as observed in non-infected animals. Although Nelfinavir treatment did not alter the expression of chemoattractant receptors or adhesion molecules on human neutrophils, in vitro migration of human neutrophils to the major human neutrophil attractant CXCL8 was augmented by this protease inhibitor. Nelfinavir appears to induce an immunomodulatory effect associated with increasing neutrophil number and functionality, which may be linked to the marked improvement in SARS-CoV-2 lung pathology independent of its lack of antiviral activity. Since Nelfinavir is no longer used for the treatment of HIV, we studied the effect of two other HIV protease inhibitors, namely the combination Lopinavir/Ritonavir (Kaletra™) in this model. This combination resulted in a similar protective effect as Nelfinavir against SARS-CoV2 induced lung pathology in hamsters.
MeSH term(s)	Animals ; COVID-19/drug therapy ; Cricetinae ; HIV Infections/drug therapy ; HIV Protease Inhibitors/pharmacology ; HIV Protease Inhibitors/therapeutic use ; Lopinavir/pharmacology ; Lopinavir/therapeutic use ; Lung ; Mesocricetus ; Nelfinavir/pharmacology ; Nelfinavir/therapeutic use ; RNA, Viral ; Ritonavir/therapeutic use ; SARS-CoV-2
Chemical Substances	HIV Protease Inhibitors ; RNA, Viral ; Lopinavir (2494G1JF75) ; Nelfinavir (HO3OGH5D7I) ; Ritonavir (O3J8G9O825)
Language	English
Publishing date	2022-04-04
Publishing country	Netherlands
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	306628-9
ISSN	1872-9096 ; 0166-3542
ISSN (online)	1872-9096
ISSN	0166-3542
DOI	10.1016/j.antiviral.2022.105311
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Article ; Online: The combined treatment of Molnupiravir and Favipiravir results in a potentiation of antiviral efficacy in a SARS-CoV-2 hamster infection model.

EBioMedicine

2021 Volume 72, Page(s) 103595

Abstract: Background: Favipiravir and Molnupiravir, orally available antivirals, have been reported to exert antiviral activity against SARS-CoV-2. First efficacy data have been recently reported in COVID-19 patients.: Methods: We here report on the combined ... ...

Abstract	Background: Favipiravir and Molnupiravir, orally available antivirals, have been reported to exert antiviral activity against SARS-CoV-2. First efficacy data have been recently reported in COVID-19 patients. Methods: We here report on the combined antiviral effect of both drugs in a SARS-CoV-2 Syrian hamster infection model. The infected hamsters were treated twice daily with the vehicle (the control group) or a suboptimal dose of each compound or a combination of both compounds. Findings: When animals were treated with a combination of suboptimal doses of Molnupiravir and Favipiravir at the time of infection, a marked combined potency at endpoint is observed. Infectious virus titers in the lungs of animals treated with the combination are reduced by ∼5 log10 and infectious virus are no longer detected in the lungs of >60% of treated animals. When start of treatment was delayed with one day a reduction of titers in the lungs of 2.4 log10 was achieved. Moreover, treatment of infected animals nearly completely prevented transmission to co-housed untreated sentinels. Both drugs result in an increased mutation frequency of the remaining viral RNA recovered from the lungs of treated animals. In the combo-treated hamsters, an increased frequency of C-to-T mutations in the viral RNA is observed as compared to the single treatment groups which may explain the pronounced antiviral potency of the combination. Interpretation: Our findings may lay the basis for the design of clinical studies to test the efficacy of the combination of Molnupiravir/Favipiravir in the treatment of COVID-19. Funding: stated in the acknowledgment.
MeSH term(s)	Amides/pharmacology ; Amides/therapeutic use ; Animals ; Antiviral Agents/pharmacology ; Antiviral Agents/therapeutic use ; COVID-19/drug therapy ; COVID-19/transmission ; Cytidine/analogs & derivatives ; Cytidine/pharmacology ; Cytidine/therapeutic use ; Disease Models, Animal ; Drug Therapy, Combination ; Female ; Hydroxylamines/pharmacology ; Hydroxylamines/therapeutic use ; Lung/virology ; Mesocricetus ; Pyrazines/pharmacology ; Pyrazines/therapeutic use ; RNA, Viral ; Treatment Outcome ; Viral Load
Chemical Substances	Amides ; Antiviral Agents ; Hydroxylamines ; Pyrazines ; RNA, Viral ; Cytidine (5CSZ8459RP) ; favipiravir (EW5GL2X7E0) ; molnupiravir (YA84KI1VEW)
Language	English
Publishing date	2021-09-24
Publishing country	Netherlands
Document type	Journal Article
ZDB-ID	2851331-9
ISSN	2352-3964
ISSN (online)	2352-3964
DOI	10.1016/j.ebiom.2021.103595
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