Skip to main content
Top
Published in: Inflammopharmacology 3/2019

01-06-2019 | Cytokines | Original Article

Anti-inflammatory properties of Liposome-encapsulated clodronate or Anti-Ly6G can be modulated by peripheral or central inflammatory markers in carrageenan-induced inflammation model

Authors: Tufan Mert, Mehmet Sahin, Emel Sahin, Selma Yaman

Published in: Inflammopharmacology | Issue 3/2019

Login to get access

Abstract

Overproduction of inflammatory markers by immune cells, such as macrophages and neutrophils, is one of the main reasons for many inflammatory conditions and inhibiting or suppressing of their production by cell depletion may provide new therapeutic targets or approaches to prevent a variety of inflammatory conditions. In this study, we examined the possible effects of anti-Ly6G-mediated systemic neutrophil depletion and liposome-encapsulated clodronate (LEC)-mediated systemic macrophage depletion on the inflammatory signs (thermal hyperalgesia, mechanical allodynia, oedema and fever) and measured the levels of various inflammation markers (tumour necrosis factor-α (TNF-α), interleukins (IL)-1β, IL-4, IL-10, macrophage inflammatory protein-1 alpha (MIP-1α/CCL3) and myeloperoxidase (MPO) in paw and spinal cord tissues in carrageenan (CG)-induced hindpaw inflammation model in rats. CG injection into the paw caused inflammation characterized by redness, swelling, heat and pain hypersensitivities. Anti-Ly6G or LEC significantly ameliorated the pain behaviours, and decreased the oedema and fever. Efficacies of anti-Ly6G or LEC on inflammatory responses changed depend on the degree of inhibition in inflammatory markers of inflamed paw or spinal cord. Anti-inflammatory properties of anti-Ly6G or LEC suggest that macrophages and/or neutrophil-mediated inflammatory cascade in inflamed site and spinal cord which can play key roles in inflammatory pain responses. These systemic or peripheral inflammatory mediators may be therapeutic targets in the treatment of many inflammatory conditions and related various diseases.
Literature
go back to reference Aratani Y (2018) Myeloperoxidase: its role for host defense, inflammation, and neutrophil function. Arch Biochem Biophys 640:47–52CrossRefPubMed Aratani Y (2018) Myeloperoxidase: its role for host defense, inflammation, and neutrophil function. Arch Biochem Biophys 640:47–52CrossRefPubMed
go back to reference Bruhn KW, Dekitani K, Nielsen TB, Pantapalangkoor P, Spellberg B (2015) Ly6G-mediated depletion of neutrophils is dependent on macrophages. Results Immunol 6:5–7CrossRefPubMedPubMedCentral Bruhn KW, Dekitani K, Nielsen TB, Pantapalangkoor P, Spellberg B (2015) Ly6G-mediated depletion of neutrophils is dependent on macrophages. Results Immunol 6:5–7CrossRefPubMedPubMedCentral
go back to reference Bucher K, Schmitt F, Autenrieth SE, Dillmann I, Nürnberg B, Schenke- Layland K, Beer-Hammer S (2015) Fluorescent Ly6G antibodies determine macrophage phagocytosis of neutrophils and alter the retrieval of neutrophils in mice. J Leukoc Biol 98:365–372CrossRefPubMed Bucher K, Schmitt F, Autenrieth SE, Dillmann I, Nürnberg B, Schenke- Layland K, Beer-Hammer S (2015) Fluorescent Ly6G antibodies determine macrophage phagocytosis of neutrophils and alter the retrieval of neutrophils in mice. J Leukoc Biol 98:365–372CrossRefPubMed
go back to reference Duque GA, Descoteaux A (2014) Macrophage cytokines: involvement in immunity and infectious diseases. Front Immunol 5:491 Duque GA, Descoteaux A (2014) Macrophage cytokines: involvement in immunity and infectious diseases. Front Immunol 5:491
go back to reference Fox S, Leitch AE, Duffin R, Haslett C, Rossi AG (2010) Neutrophil apoptosis: relevance to the innate immune response and inflammatory disease. J Innate Immun 2(3):216–227CrossRefPubMedPubMedCentral Fox S, Leitch AE, Duffin R, Haslett C, Rossi AG (2010) Neutrophil apoptosis: relevance to the innate immune response and inflammatory disease. J Innate Immun 2(3):216–227CrossRefPubMedPubMedCentral
go back to reference Ginhoux F, Jung S (2014) Monocytes and macrophages: developmental pathways and tissue homeostasis. Nat Rev Immunol 14(6):392–404CrossRefPubMed Ginhoux F, Jung S (2014) Monocytes and macrophages: developmental pathways and tissue homeostasis. Nat Rev Immunol 14(6):392–404CrossRefPubMed
go back to reference Hua S, Cabot PJ (2010) Mechanisms of peripheral immune-cell-mediated analgesia in inflammation: clinical and therapeutic implications. Trends Pharmacol Sci 31:427–433CrossRefPubMed Hua S, Cabot PJ (2010) Mechanisms of peripheral immune-cell-mediated analgesia in inflammation: clinical and therapeutic implications. Trends Pharmacol Sci 31:427–433CrossRefPubMed
go back to reference Kawanishi N, Mizokami T, Niihara H, Yada K, Suzuki K (2015) Macrophage depletion by clodronate liposome attenuates muscle injury and inflammation following exhaustive exercise. Biochem Biophys Rep 5:146–151PubMedPubMedCentral Kawanishi N, Mizokami T, Niihara H, Yada K, Suzuki K (2015) Macrophage depletion by clodronate liposome attenuates muscle injury and inflammation following exhaustive exercise. Biochem Biophys Rep 5:146–151PubMedPubMedCentral
go back to reference Kolaczkowska E, Kubes P (2013) Neutrophil recruitment and function in health and inflammation. Nat Rev Immunol 13:159–175CrossRefPubMed Kolaczkowska E, Kubes P (2013) Neutrophil recruitment and function in health and inflammation. Nat Rev Immunol 13:159–175CrossRefPubMed
go back to reference Lemmer S, Schiesser P, Geis C, Sommer C, Vanegas H, Üçeyler N (2015) Enhanced spinal neuronal responses as a mechanism for the increased nociceptive sensitivity of interleukin-4 deficient mice. Exp Neurol 271:198–204CrossRefPubMed Lemmer S, Schiesser P, Geis C, Sommer C, Vanegas H, Üçeyler N (2015) Enhanced spinal neuronal responses as a mechanism for the increased nociceptive sensitivity of interleukin-4 deficient mice. Exp Neurol 271:198–204CrossRefPubMed
go back to reference Llorian-Salvador M, Gonzalez-Rodriguez S, Lastra A, Fernandez-Garcia MT, Hidalgo A, Menendez L, Baamonde A (2016) Involvement of CC Chemokine Receptor 1 and CCL3 in Acute and Chronic Inflammatory Pain in Mice. Basic Clin Pharmacol Toxicol 119(1):32–40CrossRefPubMed Llorian-Salvador M, Gonzalez-Rodriguez S, Lastra A, Fernandez-Garcia MT, Hidalgo A, Menendez L, Baamonde A (2016) Involvement of CC Chemokine Receptor 1 and CCL3 in Acute and Chronic Inflammatory Pain in Mice. Basic Clin Pharmacol Toxicol 119(1):32–40CrossRefPubMed
go back to reference Mert T, Gunay I, Ocal I, Guzel AI, Inal TC, Sencar L, Polat S (2009) Macrophage depletion delays progression of neuropathic pain in diabetic animals. Naunyn Schmiedebergs Arch Pharmacol 379:445–452CrossRefPubMed Mert T, Gunay I, Ocal I, Guzel AI, Inal TC, Sencar L, Polat S (2009) Macrophage depletion delays progression of neuropathic pain in diabetic animals. Naunyn Schmiedebergs Arch Pharmacol 379:445–452CrossRefPubMed
go back to reference Mert T, Ocal I, Gunay I (2014a) Pain relieving effects of pulsed magnetic fields in a rat model of carrageenan-induced hindpaw inflammation. Int J Rad Biol 90(1):95–103CrossRefPubMed Mert T, Ocal I, Gunay I (2014a) Pain relieving effects of pulsed magnetic fields in a rat model of carrageenan-induced hindpaw inflammation. Int J Rad Biol 90(1):95–103CrossRefPubMed
go back to reference Mert T, Tugtag B, Kilinc M, Sahin E, Oksuz H, Gunes Y (2014b) Preventive and therapeutic effects of a beta adrenoreceptor agonist, dobutamine, in carrageenan-induced inflammatory nociception in rats. Inflammation 90(1):95–103 Mert T, Tugtag B, Kilinc M, Sahin E, Oksuz H, Gunes Y (2014b) Preventive and therapeutic effects of a beta adrenoreceptor agonist, dobutamine, in carrageenan-induced inflammatory nociception in rats. Inflammation 90(1):95–103
go back to reference Miller RJ, Jung H, Bhangoo SK, White FA (2009) Cytokine and chemokine regulation of sensory neuron function. Handb Exp Pharmacol 194:417–449CrossRef Miller RJ, Jung H, Bhangoo SK, White FA (2009) Cytokine and chemokine regulation of sensory neuron function. Handb Exp Pharmacol 194:417–449CrossRef
go back to reference Prame Kumar K, Nicholls AJ, Wong CHY (2018) Partners in crime: neutrophils and monocytes/macrophages in inflammation and disease. Cell Tissue Res 371(3):551–565CrossRefPubMedPubMedCentral Prame Kumar K, Nicholls AJ, Wong CHY (2018) Partners in crime: neutrophils and monocytes/macrophages in inflammation and disease. Cell Tissue Res 371(3):551–565CrossRefPubMedPubMedCentral
go back to reference Raoof R, Willemen HLDM, Eijkelkamp N (2018) Divergent roles of immune cells and their mediators in pain. Rheumatology (Oxford) 57(3):429–440CrossRef Raoof R, Willemen HLDM, Eijkelkamp N (2018) Divergent roles of immune cells and their mediators in pain. Rheumatology (Oxford) 57(3):429–440CrossRef
go back to reference Rittner HL, Machelska H, Stein C (2005) Leukocytes in the regulation of pain and analgesia. J Leukoc Biol 78:1215–1222CrossRefPubMed Rittner HL, Machelska H, Stein C (2005) Leukocytes in the regulation of pain and analgesia. J Leukoc Biol 78:1215–1222CrossRefPubMed
go back to reference Serhan CN, Savill J (2005) Resolution of inflammation: the beginning programs the end. Nat Immunol 6(12):1191–1197CrossRefPubMed Serhan CN, Savill J (2005) Resolution of inflammation: the beginning programs the end. Nat Immunol 6(12):1191–1197CrossRefPubMed
go back to reference Steen-Louws C, Hartgring SAY, Popov-Celeketic J, Lopes AP, de Smet MBM, Eijkelkamp N, Lafeber FPJG, Hack CE, van Roon JAG (2016) IL4-10 fusion protein is a novel drug to treat persistent inflammatory pain. J Neurosci 36:7353–7363CrossRefPubMedPubMedCentral Steen-Louws C, Hartgring SAY, Popov-Celeketic J, Lopes AP, de Smet MBM, Eijkelkamp N, Lafeber FPJG, Hack CE, van Roon JAG (2016) IL4-10 fusion protein is a novel drug to treat persistent inflammatory pain. J Neurosci 36:7353–7363CrossRefPubMedPubMedCentral
go back to reference Suo J, Linke B, Meyer dos Santos S, Pierre S, Stegner D, Zhang DD, Denis CV, Geisslinger G, Nieswandt B, Scholich K (2014) Neutrophils mediate edema formation but not mechanical allodynia during zymosan-induced inflammation. J Leukoc Biol 96(1):133–142CrossRefPubMed Suo J, Linke B, Meyer dos Santos S, Pierre S, Stegner D, Zhang DD, Denis CV, Geisslinger G, Nieswandt B, Scholich K (2014) Neutrophils mediate edema formation but not mechanical allodynia during zymosan-induced inflammation. J Leukoc Biol 96(1):133–142CrossRefPubMed
go back to reference Tejada MA, Montilla-Garcia A, Cronin SJ, Cikes D, Sanchez-Fernandez C, Gonzalez-Cano R, Ruiz-Cantero MC, Penninger JM, Vela JM, Baeyens JM, Cobos EJ (2017) Sigma-1 receptors control immune-driven peripheral opioid analgesia during inflammation in mice. Proc Natl Acad Sci USA 114(31):8396–8401CrossRefPubMed Tejada MA, Montilla-Garcia A, Cronin SJ, Cikes D, Sanchez-Fernandez C, Gonzalez-Cano R, Ruiz-Cantero MC, Penninger JM, Vela JM, Baeyens JM, Cobos EJ (2017) Sigma-1 receptors control immune-driven peripheral opioid analgesia during inflammation in mice. Proc Natl Acad Sci USA 114(31):8396–8401CrossRefPubMed
go back to reference Willemen HL, Eijkelkamp N, Garza Carbajal A, Wang H, Mack M, Zijlstra J, Heijnen CJ, Kavelaars A (2014) Monocytes/macrophages control resolution of transient inflammatory pain. J Pain 15(5):496–506CrossRefPubMedPubMedCentral Willemen HL, Eijkelkamp N, Garza Carbajal A, Wang H, Mack M, Zijlstra J, Heijnen CJ, Kavelaars A (2014) Monocytes/macrophages control resolution of transient inflammatory pain. J Pain 15(5):496–506CrossRefPubMedPubMedCentral
Metadata
Title
Anti-inflammatory properties of Liposome-encapsulated clodronate or Anti-Ly6G can be modulated by peripheral or central inflammatory markers in carrageenan-induced inflammation model
Authors
Tufan Mert
Mehmet Sahin
Emel Sahin
Selma Yaman
Publication date
01-06-2019
Publisher
Springer International Publishing
Keyword
Cytokines
Published in
Inflammopharmacology / Issue 3/2019
Print ISSN: 0925-4692
Electronic ISSN: 1568-5608
DOI
https://doi.org/10.1007/s10787-019-00563-y

Other articles of this Issue 3/2019

Inflammopharmacology 3/2019 Go to the issue