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Cytokines are a category of signaling molecules that are used extensively in cellular communication. These are made up of large and diverse family of polypeptide regulators that are produced widely throughout the body by cells of diverse embryological origin. Cytokines participate in many physiological processes including the regulation of immune and inflammatory responses. Cytokines include chemokines, interferons, interleukins, lymphokines, tumor necrosis factor but generally not hormones or growth factors. Cytokines are produced by a broad range of cells, including immune cells like macrophages, B lymphocytes, T lymphocytes and mast cells, as well as endothelial cells, fibroblasts, and various stromal cells.They act through receptors, and are especially important in the immune system, cytokines modulate the balance between humoral and cell-based immune responses and they regulate the maturation, growth, and responsiveness of particular cell populations. Cytokines are also serving as cell-signaling protein molecules used extensively in intercellular communication. Cytokines can be classified as proteins, peptides, or glycoproteins. Each cytokine has a matching cell-surface receptor; its activation leads to cascades of intracellular signaling that alter cell functions. This may include the up regulation and/or down regulation of several genes and their transcription factors, resulting in the production of other cytokines, an increase in the number of surface receptors for other molecules, or the suppression of their own effect by feedback inhibition.


Cytokines cell signaling Immune response Receptor Diagnosis Treatment

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Vinjavarapu. L. Anusha, G. Sudhakara rao, Manegar Akhleela, D. Lakshmi, M. Praharsha, K. Sofiya, B. Ramadevi, B. Navya, & Ch. Anjaneya reddy. (2024). The Physiological Role Of Cytokines In Inflammation And Immune Response. International Journal of Research in Pharmacology & Pharmacotherapeutics, 13(2), 92-100. Retrieved from


  1. 1. Weaver CT, Hatton RD, Mangan PR, Harrington LE. IL-17 family cytokines and the expanding diversity of effector T cell lineages. Annu Rev Immunol. 2007; 25: 821-852.
  2. 2. Watford WT, Moriguchi M, Morinobu A, O’Shea JJ. The biology of IL-12: coordinating innate and adaptive immune responses. Cytokine Growth Factor Rev. 2003; 14: 361-368.
  3. 3. Lackie J. Cytokine. John Lackie, editor. In: A Dictionary of Biomedicine. UK: Oxford University Press. 2010.
  4. 4. Ibelgaufts H. Cytokines. In: Cytokines & Cells Online Pathfinder Encyclopedia. 2013.
  5. 5. Schulte W, Bernhagen J, Bucala R. Cytokines in sepsis: potent immunoregulators and potential therapeutic targets--an updated view. Mediators Inflamm. 2013; 2013: 165974.
  6. 6. Kierszenbaum F, Sztein M. Chagas’ disease (American trypanosomiasis). Kierszenbaum F, Editor. In: Parasitic Infections and the Immune System. San Diego: Academic Press. 1994; 53-85.
  7. 7. Graves DT, Jiang Y. Chemokines, a family of chemotactic cytokines. Crit Rev Oral Biol Med. 1995; 6: 109-118.
  8. 8. Stow JL, Murray RZ. Intracellular trafficking and secretion of inflammatory cytokines. Cytokine Growth Factor Rev. 2013; 24: 227-239.
  9. 9. Van der Meide PH, Schellekens H. Cytokines and the immune response. Biotherapy. 1996; 8: 243-249.
  10. 10. Mousa A, Bakhiet M. Role of cytokine signaling during nervous system development. Int J Mol Sci. 2013; 14: 13931-13957.
  11. 11. Akira S, Takeda K. Toll-like receptor signalling. Nat Rev Immunol. 2004; 4: 499-511.
  12. 12. Miller AH, Maletic V, Raison CL. Inflammation and its discontents: the role of cytokines in the pathophysiology of major depression. Biol Psychiatry. 2009; 65: 732-741.
  13. 13. Boundless. Types of Cytokines Participating in Immune Response. Boundless Anatomy and Physiology. Boundless. 2014.
  14. 14. Platanias LC. Mechanisms of type-I- and type-II-interferon-mediated signalling. Nat Rev Immunol. 2005; 5: 375-386.
  15. 15. David JR. Delayed hypersensitivity in vitro: its mediation by cell-free substances formed by lymphoid cell-antigen interaction. Proc Natl Acad Sci U S A. 1966; 56: 72-77.
  16. 16. Bloom BR, Bennett B. Mechanism of a reaction in vitro associated with delayed-type hypersensitivity. Science. 1966; 153: 80- 82.
  17. 17. Bloom BR, Bennett B. Relation of the migration inhibitory factor (MIF) to delayed-type hypersensitivity reactions. Ann N Y Acad Sci. 1970; 169: 258-265.
  18. 18. Hamblin AS. Lymphokines and interleukins. Immunology. 1988; 64: 39–41.
  19. 19. Rithidech KN, Lai X, Honikel L, Reungpatthanaphong P, Witzmann FA. Identification of proteins secreted into the medium by human lymphocytes irradiated in vitro with or without adaptive environments. Health Phys. 2012; 102: 39-53.
  20. 20. Kouttab NM, Mehta S, Morgan J, Tannir N, Sahasrabuddhe C. Lymphokines and monokines as regulators of human lymphoproliferation. Clin Chem. 1984; 30: 1539-1545.
  21. 21. Smith JA, Das A, Ray SK, Banik NL. Role of pro-inflammatory cytokines released from microglia in neurodegenerative diseases. Brain Res Bull. 2012; 87: 10-20.
  22. 22. Zhang JM, An J. Cytokines, inflammation, and pain. Int Anesthesiol Clin. 2007; 45: 27-37. 23.
  23. 23. Koneru R, Hotte SJ. Role of cytokine therapy for renal cell carcinoma in the era of targeted agents. Curr Oncol. 2009; 16 Suppl 1: S40-44.
  24. 24. Dinarello CA. Historical insights into cytokines. Eur J Immunol. 2007; 37 Suppl 1: S34-45. 25.
  25. 25. Bai X, Kinney WH, Su WL, Bai A, Ovrutsky AR, et al. Caspase-3-independent apoptotic pathways contribute to interleukin32?-mediated control of Mycobacterium tuberculosis infection in THP-1 cells. BMC Microbiol. 2015; 15: 39.
  26. 26. Gery I, Gershon RK, Waksman BH. Potentiation of the T-lymphocyte response to mitogens. I. The responding cell. J Exp Med. 1972; 136: 128-142.
  27. 27. Colić M, Jandrić D, Gasić S, Vucević D, Popović P. Immunosine (7-thia-8-oxoguanosine) acts as a cofactor for proliferation of T cells. Fundam Clin Pharmacol. 2000; 14: 209-217.
  28. 28. Mier JW, Gallo RC. Purification and some characteristics of human T-cell growth factor from phytohemagglutinin-stimulated lymphocyte-conditioned media. Proc Natl Acad Sci U S A. 1980; 77: 6134-6138.
  29. 29. Liles WC, Van Voorhis WC. Review: nomenclature and biologic significance of cytokines involved in inflammation and the host immune response. J Infect Dis. 1995; 172: 1573-1580.
  30. 30. Coussens LM, Werb Z. Inflammation and cancer. Nature. 2002; 420: 860-867.
  31. 31. Cohen MC, Cohen S. Cytokine function: a study in biologic diversity. Am J Clin Pathol. 1996; 105: 589-598.
  32. 32. Tisoncik JR, Korth MJ, Simmons CP, Farrar J, Martin TR. Into the eye of the cytokine storm. Microbiol Mol Biol Rev. 2012; 76: 16-32.
  33. 33. Bodmer MW, Henderson B. Therapeutic Modulation of Cytokines. 1996.
  34. 34. Tönges L, Schlachetzki JC, Weishaupt JH, Bähr M. Hematopoietic cytokines--on the verge of conquering neurology. Curr Mol Med. 2007; 7: 157-170.
  35. 35. Rozwarski DA, Gronenborn AM, Clore GM, Bazan JF, Bohm A. Structural comparisons among the short-chain helical cytokines. Structure. 1994; 2: 159-173.
  36. 36. Ouaguia L, Mrizak D, Renaud S, Moralès O, Delhem N2. Control of the inflammatory response mechanisms mediated by natural and induced regulatory T-cells in HCV-, HTLV-1-, and EBV-associated cancers. Mediators Inflamm. 2014; 2014: 564296.
  37. 37. Jin Y, Mailloux CM, Gowan K, Riccardi SL, LaBerge G. NALP1 in vitiligo-associated multiple autoimmune disease. N Engl J Med. 2007; 356: 1216-1225.
  38. 38. Choi AM, Alam J. Heme oxygenase-1: function, regulation, and implication of a novel stress-inducible protein in oxidantinduced lung injury. Am J Respir Cell Mol Biol. 1996; 15: 9-19.
  39. 39. Vlahopoulos S, Boldogh I, Casola A, Brasier AR, Boldogh, et al. Nuclear factor-kappaB-dependent induction of interleukin-8 gene expression by tumor necrosis factor alpha: evidence for an antioxidant sensitive activating pathway distinct from nuclear translocation. Blood. 1999; 94:1878–1889.
  40. 40. David F, Farley J, Huang H, Lavoie JP, Laverty S. Cytokine and chemokine gene expression of IL-1beta stimulated equine articular chondrocytes. Vet Surg. 2007; 36: 221-227.
  41. 41. Carpenter LR, Moy JN, Roebuck KA. Respiratory syncytial virus and TNF alpha induction of chemokine gene expression involves differential activation of Rel A and NF-kappa B1. BMC Infect Dis. 2002; 2: 5.
  42. 42. Tian B, Nowak DE, Brasier AR. A TNF-induced gene expression program under oscillatory NF-kappaB control. BMC Genomics. 2005; 6: 137.
  43. 43. Chokkalingam V, Tel J, Wimmers F, Liu X, Semenov S. Probing cellular heterogeneity in cytokine-secreting immune cells using droplet-based microfluidics. Lab Chip. 2013; 13: 4740-4744.
  44. 44. Bhatia S, Tykodi SS, Thompson JA. Treatment of metastatic melanoma: an overview. Oncology (Williston Park). 2009; 23: 488-496.
  45. 45. Trinchieri G. Interleukin-12: a proinflammatory cytokine with immunoregulatory functions that bridge innate resistance and antigen-specific adaptive immunity. Annu Rev Immunol. 1995; 13: 251-276.
  46. 46. Liu VC, Wong LY, Jang T, Shah AH, Park I. Tumor evasion of the immune system by converting CD4+CD25- T cells into CD4+CD25+ T regulatory cells: role of tumor-derived TGF-beta. J Immunol. 2007; 178: 2883-2892.
  47. 47. Masihi KN. Fighting infection using immunomodulatory agents. Expert Opin Biol Ther. 2001; 1: 641-653.
  48. 48. Borovikova LV, Ivanova S, Zhang M, Yang H, Botchkina GI. Vagus nerve stimulation attenuates the systemic inflammatory response to endotoxin. Nature. 2000; 405: 458-462.
  49. 49. Sen GC. Viruses and interferons. Annu Rev Microbiol. 2001; 55: 255-281.
  50. 50. Yang XY, Wang LH, Farrar WL. A Role for PPAR γ in the Regulation of Cytokines in Immune Cells and Cancer. PPAR Res. 2015; 982750.
  51. 51. Aslani F, Schuppe HC, Guazzone VA, Bhushan S, Wahle E. Targeting high mobility group box protein 1 ameliorates testicular inflammation in experimental autoimmune orchitis. Hum Reprod. 2015; 30: 417-431.
  52. 52. Akdis M, Burgler S, Crameri R, Eiwegger T, Fujita H. Interleukins, from 1 to 37, and interferon-γ: receptors, functions, and roles in diseases. J Allergy Clin Immunol. 2011; 127: 701-721.
  53. 53. Mogensen TH. Pathogen recognition and inflammatory signaling in innate immune defenses. Clin Microbiol Rev. 2009; 22: 240-273, Table of Contents.
  54. 54. Janeway CA Jr, Medzhitov R. Innate immune recognition. Annu Rev Immunol. 2002; 20: 197-216.
  55. 55. Rankin JA. Biological mediators of acute inflammation. AACN Clin Issues. 2004; 15: 3-17.
  56. 56. Dinarello CA. Immunological and inflammatory functions of the interleukin-1 family. Annu Rev Immunol. 2009; 27: 519-550.
  57. 57. Rollins BJ. Chemokines. Blood. 1997; 90: 909-928.
  58. 58. Opal SM, DePalo VA. Anti-inflammatory cytokines. Chest. 2000; 117: 1162-1172.
  59. 59. Moore KW, de Waal Malefyt R, Coffman RL, O’Garra A. Interleukin-10 and the interleukin-10 receptor. Annu Rev Immunol. 2001; 19: 683-765.
  60. 60. Trinchieri G. Interleukin-12 and the regulation of innate resistance and adaptive immunity. Nat Rev Immunol. 2003; 3: 133- 146.
  61. 61. Hunter CA, Gabriel KE, Radzanowski T, Neyer LE, Remington JS. Type I interferons enhance production of IFN-gamma by NK cells. Immunol Lett. 1997; 59: 1-5.
  62. 62. Schroder K, Hertzog PJ, Ravasi T, Hume DA. Interferon-gamma: an overview of signals, mechanisms and functions. J Leukoc Biol. 2004; 75: 163-189.
  63. 63. Salmon M, Kitas GD, Gaston JS, Bacon PA. Interleukin-2 production and response by helper T-cell subsets in man. Immunology. 1988; 65: 81-85.
  64. 64. Hwang ES, Hong JH, Glimcher LH. IL-2 production in developing Th1 cells is regulated by heterodimerization of RelA and T-bet and requires T-bet serine residue 508. J Exp Med. 2005; 202: 1289-1300