Abstract
Innate immune cells and mediators play important roles in recognizing molecular patterns of potential pathogens and unlike adaptive immune cells, the innate immune response is not antigen-specific. However, innate immune cells are critical for the early control of infection and act rapidly to alert the immune system and initiate adaptive immunity. Macrophages and neutrophils quickly respond to infectious pathogens, mediating their destruction via phagocytosis, and producing cytokines that recruit and activate immune cells. Dendritic cells play a vital role in innate and adaptive crosstalk to initiate the adaptive immune response to fight pathogens. Natural killer cells play a critical role in the control of viral infections and cancers and the modulation of macrophages and dendritic cells. Mast cells release proinflammatory mediators that induce vascular permeability and promote leukocyte recruitment. Lastly, both mast cells and granulocytes such as eosinophils and basophils defend against parasites and participate in the modulation of immune responses. While these innate immune cells and mediators are crucial in the early response to infection, the inappropriate response of the innate immune system, however, can play a role in the pathophysiology of conditions in which chronic inflammation contributes to disease symptoms and progression. In this chapter, the normal physiological role of the innate immune system and its components are discussed. Many of these mechanisms can be targeted by several drug classes which aim to suppress cytokines as well as block leukocyte recruitment in disease states in which the immune system may overreact to target self-antigens (i.e. autoimmunity).
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Abreu MT. Anti-TNF failures in Crohnās disease. Gastroenterol Hepatol. 2011;7(1):37ā9.
Bendtzen K. Immunogenicity of anti-TNF-Ī± biotherapies: I. individualized medicine based on immunopharmacological evidence. Front Immunol. 2015;6:152.
Brennan FM, Chantry D, Jackson A, Maini RN, Feldmann M. Inhibitory effect of TNF-alpha antibodies on synovial cell interleukin-1 production in rheumatoid arthritis. Lancet. 1989;334:244ā7.
Campa M, Mansouri B, Warren R, Menter A. A review of biologic therapies targeting IL-23 and IL-17 for use in moderate-to-severe plaque psoriasis. Dermatol Ther (Heidelb). 2016;6(1):1ā12.
Cessak G, Kuzawinska O, Burda A, Lis K, Wojnar M, Mirowska-Guzel D, et al. TNF inhibitorsāmechanisms of action, approved and off-label indications. Pharmacol Rep. 2014;66(5):836ā44.
Chen R, Chen B. Siltuximab (CNTO 328): a promising option for human malignancies. Drug Des Devel Ther. 2015;9:3455ā8.
Christmas P. Toll-like receptors: sensors that detect infection. Nat Educ. 2010;3(9):85.
De Paepe B, Creus KK, De Bleecker JL. The tumor necrosis factor superfamily of cytokines in the inflammatory myopathies: potential targets for therapy. Clin Dev Immunol. 2011;2012:369432.
Dinarello CA, van der Meer JWM. Treating inflammation by blocking interleukin-1 in humans. Semin Immunol. 2013;25(6):469ā84.
Doss GP, Agoramoorthy G, Chakraborty C. TNF/TNFR: drug target for autoimmune diseases and immune-mediated inflammatory diseases. Front Biosci. 2014;19:1028ā40.
DubĆ© PE, Punit S, Polk DB. Redeeming an old foe: protective as well as pathophysiological roles for tumor necrosis factor in inflammatory bowel disease. Am J Physiol Gastrointest Liver Physiol. 2015;308(3):G161ā70.
Elliott MJ, Maini RN, Feldmann M, Kalden JR, Antoni C, Smolen JS, et al. Randomised double blind comparison of a chimaeric monoclonal antibody to tumour necrosis factor-alpha (cA2) versus placebo in rheumatoid arthritis. Lancet. 1994;344:1105ā10.
Feldmann M, Maini RN. Anti-TNF-alpha therapy of rheumatoid arthritis: what have we learned? Ann Rev Immunol. 2001;19:163ā96.
Feldmann M, Brennan FM, Maini RN. Role of cytokines in rheumatoid arthritis. Ann Rev Immunol. 1996;14:397ā440.
Giancane G, Minoia F, DavƬ S, Bracciolini G, Consolaro A, Ravelli A. IL-1 inhibition in systemic juvenile idiopathic arthritis. Front Pharmacol. 2016;7:467.
Goldback-Mansky R. Blocking interleukin-1 in rheumatic diseases. Ann N Y Acad Sci. 2009;1182:111ā23.
Gonzalez-Navajas JM, Lee J, David M, Raz E. Immunomodulatory functions of type I IFNs. Nat Rev Immunol. 2012;12:125ā35.
Haanstra KG, Hofman SO, Lopes EstĆŖvĆ£o DM, Blezer EL, Bauer J, Yang LL. Antagonizing the Ī±4Ī²1 integrin, but not Ī±4Ī²7, inhibits leukocytic infiltration of the central nervous system in rhesus monkey experimental autoimmune encephalomyelitis. J Immunol. 2013;190(5):1961ā73.
Heinrich PC, Behrmann I, Muller-Newen G, Schaper F, Graeve L. Interleukin-6-type cytokine signaling through the gp130/JAK/STAT pathway. Biochem J. 1998;334:297ā314.
Hennigan S, Kavanaugh A. Interleukin-6 inhibitors in the treatment of rheumatoid arthritis. Ther Clin Risk Manag. 2008;4(4):767ā75.
Kalliolias GD, Ivashkiv LB. TNF biology, pathogenic mechanisms and emerging therapeutic strategies. Nat Rev Rheum. 2016;12:49ā62.
Kim GW, Lee NR, Pi RH, Lim YS, Lee YM, Lee JM. IL-6 inhibitors for treatment of rheumatoid arthritis: past, present, and future. Arch Pharm Res. 2015;38(5):575ā84.
Kishimoto J, Akira S, Taga T. IL-6 receptor mechanism of signal transduction. Int J Immunopharmacol. 1992;14:431ā8.
Lukina GV, Sigidin Ya A. Certolizumab in therapy of rheumatoid arthritis. Sovrem Revmatol. 2012;2:44ā9.
Mayadas TN, Culler X, Lowell CA. The multifaceted functions of neutrophils. Annu Rev Pathol. 2014;9:181ā218.
Mclean LP, Shea-Donahue T, Cross RK. Vedolizumab for the treatment of ulcerative colitis and Crohnās disease. Immunotherapy. 2012;4(9):883ā98.
Mihara M, Hashizume M, Yoshida H, Suzuki M, Shiina M. IL-6/IL-6 receptor system and its role in physiological and pathological conditions. Clin Sci. 2012;122(4):143ā59.
Mosser DM, Edwards JP. Exploring the full spectrum of macrophage activation. Nat Rev Immunol. 2008;8(12):958ā69.
Orrock JE, Ilowite NT. Canakinumab for the treatment of active systemic juvenile idiopathic arthritis. Expert Rev Clin Pharmacol. 2016;9(8):1015ā24.
Perry AK. The host type I interferon response to viral and bacterial infections. Nat Cell Res. 2005;15(6):407ā22.
Shealy D, Cai A, Staquet K, Baker A, Lacy ER, Johns L, et al. Characterization of golimumab, a human monoclonal antibody specific for human tumor necrosis factor Ī±. MAbs. 2010;2:428ā39.
Spooner CE, Markowitz NP, Saravolatz LD. The role of tumor necrosis factor in sepsis. Clin Immunol Immunopathol. 1992;62(1 Pt 2):S11ā7.
Stone KD, Prussin C, Metcalfe DD. IgE, mast cells, basophils, and eosinophils. J Allergy Clin Immunol. 2010;125(2 Suppl 2):S73ā80.
Taylor P. Developing anti-TNF and biology agents. The past, the present, and the future. Rheumatology. 2011;50(8):1351ā3.
Trinchieri G. Interleukin-12: a proinflammatory cytokine with immunoregulatory functions that bridge innate resistance and antigen-specific adaptive immunity. Annu Rev Immunol. 1995;12:251ā76.
Wajant H, et al. Tumor necrosis factor signaling. Cell Death Differ. 2003;10(1):45ā65.
Zhang JM, An J. Cytokines, inflammation and pain. Int Anesthes Clin. 2007;45(2):27ā37.
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Szollosi, D.E., Mathias, C.B. (2020). Modulation of theĀ Innate Immune System. In: Mathias, C., McAleer, J., Szollosi, D. (eds) Pharmacology of Immunotherapeutic Drugs. Springer, Cham. https://doi.org/10.1007/978-3-030-19922-7_2
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DOI: https://doi.org/10.1007/978-3-030-19922-7_2
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