Immunopharmacological aspects of the cytokine system
https://doi.org/10.20538/1682-0363-2019-1-84-95
Abstract
Cytokines represent a unique family of endogenous polypeptide mediators of intercellular interaction. From an immunopharmacological point of view cytokines can be marked out as a new, separate immunoregulatory molecule system and have some common biochemical properties and pleiotropic type of biological activity. In the cytokine regulatory system both reduction and elevation of cytokine levels can cause pathology. Several endogenous systems exist to control cytokine elevation and prevent tissue pathology. When synthesized simultaneously, cytokines form a cytokine chain. Deletion of any unit of this chain leads to the break in the formation of immunopathology. Cytokines as therapeutic preparations have evident advantages but also some limitations such as pharmacokinetics with short circulation period, adverse effects due to pleiotropic mode of action, and injectable drug forms. Rational design for clinical cytokine application could be linked with the development of prolonged and local drug forms or personalized cytokine therapy.
About the Author
A. S. SimbirtsevRussian Federation
Simbirtsev Andrey S., Simbirtsev Andrey S., DM, Professor, Corresponding Member of RAS, Scientific Supervisor, State Research Institute of Highly Pure Biopreparations
7, Pudozhskaya Str., St. Petersburg, 197110
References
1. Simbirtsev A.S. Cytokines in the pathogenesis and therapy of human diseases. St. Petersburg: Foliant Publ., 2018: 512 (in Russ.).
2. Sankaran V.G., Weiss M.J. Anemia: progress in molecular mechanisms and therapies. Nat. Med. 2015; 21 (3): 221–230. DOI: 10.1038/nm.3814.
3. Brines M., Cerami A. Discovering erythropoietin’s extra-hematopoietic functions: biology and clinical promise. Kidney Int. 2006; 70 (2): 246–250. DOI: 10.1038/sj.ki.5001546.
4. Lyman G. Pegfilgrastim: a granulocyte colony-stimulating factor with sustained duration of action. Expert Opin. Biol. Ther. 2005; 5 (12): 1635–1646. DOI: 10.1517/14712598.5.12.1635.
5. Schoggins J.W., Rice C.M. Interferon-stimulated genes and their antiviral effector functions. Curr. Opin. Virol. 2011; 1 (6): 519–525. DOI: 10.1016/j.coviro.2011.10.008.
6. Molleston J.M., Cherry S. Attacked from All Sides: RNA Decay in Antiviral Defense. Viruses. 2017; 9 (1). pii: E2. DOI: 10.3390/v9010002.
7. Martinez J., Huang X., Yang Y. Direct action of type I IFN on NK cells is required for their activation in response to vaccinia viral infection in vivo. J. Immunol. 2008; 180 (3): 1592–1597. DOI: 10.4049/jimmunol.180.3.1592.
8. Lindahl P., Gresser I., Leary P., Tovey M. Interferon treatment of mice: enhanced expression of histocompatibility antigens on lymphoid cells. Proc. Natl. Acad. Sci. USA. 1976; 73 (4): 1284–1287. PMC430248.
9. Welsh R., Bahl K., Marshall H., Urban S. Type 1 interferons and antiviral CD8 T-cell responses. PLoS Pathog. 2012; 8 (1): e1002352. DOI: 10.1371/journal.ppat.1002352.2012.V.8:e1002352.
10. Srivastava S., Koch M.A., Pepper M., Campbell D.J. Type I interferons directly inhibit regulatory T cells to allow optimal antiviral T cell responses during acute LCMV infection. J. Exp. Med. 2014; 211 (5): 961–974. DOI: 10.1084/jem.20131556.
11. Simbirtsev A.S. Interleukin-1. Physiology, pathology, clinic. St. Petersburg: Foliant Publ., 2011: 480 (in Russ.).
12. Ng C.T., Oldstone M.B. IL-10: achieving balance during persistent viral infection. Curr. Top. Microbiol. Immunol. 2014; 380: 129–144. DOI: 10.1007/978-3-662-43492-5_6.
13. Tinoco R., Alcalde V., Yang Y., Sauer K, Zuniga E.I. Cell-intrinsic transforming growth factor-β signaling mediates virus-specific CD8+ T cell deletion and viral persistence in vivo. Immunity. 2009; 31 (1): 145–157. DOI: 10.1016/j.immuni.2009.06.015.
14. Wang Y., Swiecki M., Cella M., Alber G., Schreiber R.D., Gilfillan S., Colonna M. Timing and magnitude of type I interferon responses by distinct sensors impact CD8 T cell exhaustion and chronic viral infection. Cell Host Microbe. 2012; 11 (6): 631–642. DOI: 10.1016/j.chom.2012.05.003.
15. Teijaro J.R. Type I interferons in viral control and immune regulation. Curr. Opin. Virol. 2016; 16: 31–40. DOI: 10.1016/j.coviro.2016.01.001.
16. Dinarello C.A. Biological basis for interleukin-1 in disease. Blood. 1996; 87 (6): 2095–2147. PMID: 8630372
17. Tracey K.J. Physiology and immunology of the cholinergic antiinflammatory pathway. J. Clin. Invest. 2007; 117 (2): 289–296. DOI: 10.1172/JCI30555.
18. Freitas Lima L.C., Braga V.A., do Socorro de França Silva M., Cruz J.C., Sousa Santos S.H., de Oliveira Monteiro M.M., Balarini C.M. Adipokines, diabetes and atherosclerosis: an inflammatory association. Front. Physiol. 2015; 6: 304. DOI: 10.3389/fphys.2015.00304.
19. French M.A., Lenzo N., John N., Mallal S.A., McKinnon E.J., James I.R., Price P., Flexman J.P., Tay-Kearney M.L. Immune restoration disease after the treatment of immunodeficient HIV-infected patients with highly active antiretroviral therapy. HIV Med. 2000; 1 (2): 107– 115. PMID: 11737333
20. Norelli M., Camisa B., Barbiera G., Falcone L., Purevdorj A., Genua M., Sanvito F., Ponzoni M., Doglioni C., Cristofori P., Traversari C., Bordignon C., Ciceri F., Ostuni R., Bonini C., Casucci M., Bondanza A. Monocyte-derived IL-1 and IL-6 are differentially required for cytokine-release syndrome and neurotoxicity due to CAR T cells. Nat. Med. 2018; 24 (6): 739–748. DOI: 10.1038/s41591-018-0036-4.
21. Boraschi D., Tagliabue A. The interleukin-1 receptor family. Semin. Immunol. 2013; 25 (6): 394–407. DOI: 10.1016/j.smim.2013.10.023.
22. Kalliolias G.D., Ivashkiv L.V. TNF biology, pathogenic mechanisms and emerging therapeutic strategies. Nat. Rev. Rheumatol. 2016; 12 (1): 49–62. DOI: 10.1038/nrrheum.2015.169.
23. Jones S.A., Scheller J., Rose-John S. Therapeutic strategies for the clinical blockade of IL-6/gp130 signaling. J. Clin. Invest. 2011; 121 (9): 3375–3383. DOI: 10.1172/JCI57158.
24. Rubin L.A., Kurman C.C., Fritz M.E., Biddison W.E., Boutin B., Yarchoan R., Nelson D.L. Soluble interleukin-2 receptors are released from activated human lymphoid cells in vitro. J. Immunol. 1985; 135 (5): 3172– 3177. PMID: 3930598.
25. Wormald S., Hilton D.J. Inhibitors of cytokine signal transduction. J. Biol. Chem. 2004; 279 (2): 821–824. DOI: 10.1074/jbc.R300030200.
26. Hurme M., Santtila S. IL-1 receptor antagonist (IL- 1Ra) plasma levels are co-ordinately regulated by both IL-1Ra and IL-1beta genes. Eur. J. Immunol. 1998; 28 (8): 2598–2602. DOI: 10.1002/(SICI)1521-4141(199808)28:08<2598::AID-IMMU2598>3.0.CO;2-K.
27. Rudensky A. FoxP3 and dominant tolerance. Philos. Trans. R. Soc. Lond. B Biol. 2005; 360 (1461): 1645– 1646. DOI: 10.1098/rstb.2005.1731.
28. Picard C., Al-Herz W., Bousfiha A., Casanova J.L., Chatila T., Conley M.E., Cunningham-Rundles C., Etzioni A., Holland S.M., Klein C., Nonoyama S., Ochs H.D., Oksenhendler E., Puck J.M., Sullivan K.E., Tang M.L., Franco J.L., Gaspar H.B. Primary Immunodeficiency Diseases: an Update on the Classification from the International Union of Immunological Societies Expert Committee for Primary Immunodeficiency 2015. J. Clin. Immunol. 2015; 35 (8): 696–726. DOI: 10.1007/s10875-015-0201-1.
29. McDermott M., Aksentijevich I., Galon J., McDermott E.M., Ogunkolade B.W., Centola M., Mansfield E., Gadina M., Karenko L., Pettersson T., McCarthy J., Frucht D.M., Aringer M., Torosyan Y., Teppo A.M., Wilson M., Karaarslan H.M., Wan Y., Todd I., Wood G., Schlimgen R., Kumarajeewa T.R., Cooper S.M., Vella J.P., Amos C.I., Mulley J., Quane K.A., Molloy M.G., Ranki A., Powell R.J., Hitman G.A., O’Shea J.J., Kastner D.L. Germline mutations in the extracellular domains of the 55 kDa TNF receptor, TNFR1, define a family of dominantly inherited autoinflammatory syndromes. Cell. 1999; 97 (1): 133–144. PMID: 10199409.
30. Martorana D., Bonatti F., Mozzoni P., Vaglio A., Percesepe A. Monogenic Autoinflammatory Diseases with Mendelian Inheritance: Genes, Mutations, and Genotype/Phenotype Correlations. Front. Immunol. 2017; 8: 344. DOI: 10.3389/fimmu.2017.00344.
31. Hoffman H., Mueller J., Broide D., Wanderer A., Kolodner R. Mutation of a new gene encoding a putative pyrinlike protein causes familial cold autoinflammatory syndrome and Muckle-Wells syndrome. Nat. Genet. 2001; 29 (3): 301–305. DOI: 10.1038/ng756.
32. Aksentijevich I., Masters S.L., Ferguson P.J., Dancey P., Frenkel J., van Royen-Kerkhoff A., Laxer R., Tedgеrd U., Cowen E.W., Pham T.H., Booty M., Estes J.D., Sandler N.G., Plass N., Stone D.L., Turner M.L., Hill S., Butman J.A., Schneider R., Babyn P., El-Shanti H.I., Pope E., Barron K., Bing X., Laurence A., Lee C.C., Chapelle D., Clarke G.I., Ohson K., Nicholson M., Gadina M., Yang B., Korman B.D., Gregersen P.K., van Hagen P.M., Hak A.E., Huizing M., Rahman P., Douek D.C., Remmers E.F., Kastner D.L., Goldbach-Mansky R. An Autoinflammatory Disease with Deficiency of the Interleukin-1 – Receptor Antagonist. N. Engl. J. Med. 2009; 360 (23): 2426– 2437. DOI: 10.1056/NEJMoa0807865.
33. Hawkins P., Lachmann H., Aganna E., McDermott M. Spectrum of clinical features in Muckle-Wells syndrome and response to anakinra. Arthritis Rheum. 2004; 50 (2): 607–612. DOI: 10.1002/art.20033.
34. Crow Y.J. Type I interferonopathies: a novel set of inborn errors of immunity. Ann. NY Acad. Sci. 2011; 1238: 91–98. DOI: 10.1111/j.1749-6632.2011.06220.x.
35. Aicardi J., Goutières F. A progressive familial encephalopathy in infancy with calcifications of the basal ganglia and chronic cerebrospinal fluid lymphocytosis. Ann. Neurol. 1984; 15 (1): 49–54. DOI: 10.1002/ana.410150109.
36. Daien C.I., Morel J. Predictive factors of response to biological disease modifying antirheumatic drugs: towards personalized medicine. Mediators Inflamm. 2014; 2014: 386148. DOI: 10.1155/2014/386148.
37. Dennis G.Jr., Holweg C.T., Kummerfeld S.K., Choy D.F., Setiadi A.F., Hackney J.A., Haverty P.M., Gilbert H., Lin W.Y., Diehl L., Fischer S., Song A., Musselman D., Klearman M., Gabay C., Kavanaugh A., Endres J., Fox D.A., Martin F., Townsend M.J. Synovial phenotypes in rheumatoid arthritis correlate with response to biologic therapeutics. Arthritis Res. Ther. 2014; 16 (2): R90. DOI: 10.1186/ar4555.
Review
For citations:
Simbirtsev A.S. Immunopharmacological aspects of the cytokine system. Bulletin of Siberian Medicine. 2019;18(1):84-95. (In Russ.) https://doi.org/10.20538/1682-0363-2019-1-84-95