Physiological and Immunological Activity

  • Ewa Grodzinsky
  • Märta Sund Levander


Half a century ago, immunology was almost synonymous with infectious diseases and microbiology. The immune system contains various immunological cells and neurotransmitters. These cells synthesize and secrete in response to foreign agents, stress, an autoimmune reaction, or mechanical injury. There are two different branches working together: the innate and the adaptive immune systems. An increase in body temperature has been known for a very long time to be associated with ‘something not is as it should be’. Cytokines are small functional proteins that play essential roles in shaping an immune response to foreign or self-antigens. Further, they induce an increase in body temperature and stimulate the synthesis of acute-phase proteins. Research on the pathogenesis of fever is today called ‘cytokine biology’, that is, pyrogenic activity.


  1. 1.
    Medzhitov R. Origin and physiological roles of inflammation. Nature. 2008;454:428–35.CrossRefGoogle Scholar
  2. 2.
    Heinrich PC, Castell JV, Andus T. Interleukin-6 and the acute phase response. Biochem J. 1990;265(3):621–36.CrossRefGoogle Scholar
  3. 3.
    Kato T, Kitagawa S. Regulation of neutrophil functions by proinflammatory cytokines. Int J Hematol. 2006;84:205–9.CrossRefGoogle Scholar
  4. 4.
    Xing L, Remick D. Neutrophils as firemen, production of anti-inflammatory mediators by neutrophils in a mixed cell environment. Cell Immunol. 2004;231:126–32.CrossRefGoogle Scholar
  5. 5.
    Janeway CJ, Medzhitov R. Innate Immune Recognition. Annu Rev Immunol. 2002;20:196–216.Google Scholar
  6. 6.
    Shi H, Deitch E, Da Xu Z, Lu Q, Hauser C. Hypertonic saline improves intestinal mucosa barrier function and lung injury after trauma-hemorrhagic shock. Shock. 2002;17:496–501.CrossRefGoogle Scholar
  7. 7.
    Pillay J, Hietbrink F, Koenderman L, Leenen L. The systemic inflammatory response induced by trauma is reflected by multiple phenotypes of blood neutrophils. Injury. 2007;38(12):1365–72.CrossRefGoogle Scholar
  8. 8.
    Hunt K, Walsh B, Voegel D, Roberts HC. Inflammation in aging part 1: physiology and immunological mechanisms. Biol Res Nurs. 2010;11(3):245–52.CrossRefGoogle Scholar
  9. 9.
    Wikby A, Maxson P, Olsson J, Johansson B, Ferguson F. Changes in CD8 and CD4 lymphocyte subsets, T cell proliferation responses and nonsurvival in the very old: the Swedish longitudinal OCTO-immune study. Mech Aging Dev. 1998;102:187–98.CrossRefGoogle Scholar
  10. 10.
    Bowie A. A46R and A52R from vaccinia virus are antagonists of host IL-1 and toll-like receptor signaling. Proc Natl Acad Sci. 2000;97:10162–7.CrossRefGoogle Scholar
  11. 11.
    Infant-Duarte C. Microbial lipopeptides induce the production of IL-17 in TH cells. J Immunol. 2000;165:107–15.CrossRefGoogle Scholar
  12. 12.
    Ghilardi N, Quyang W. Targeting the development and effector functions of Th17 cells. Semin Immunol. 2007;19:383–93.CrossRefGoogle Scholar
  13. 13.
    Meneghin A, Hogaboam C. Infectious disease, the innate immune response, and fibrosis. J Clin Invest. 2007;117(3):530–8.CrossRefGoogle Scholar
  14. 14.
    Gamble K, Berry R, Frank S, Young M. Circadian clock control of endocrine factors. Nat Rev Endocrinol. 2014;10(8):466–75.CrossRefGoogle Scholar
  15. 15.
    Skwarlo-Sonta K. Melatonin in immunity: comparative aspects. Neuroendocrinol Lett. 2002;23:61–6.Google Scholar
  16. 16.
    Hori S. Control of regulatory T cell development by the transcription factor FOXp3. Science. 2003;299:1057–61.CrossRefGoogle Scholar
  17. 17.
    Valencia, J, Watabe, H, Chi, A, Rouzaud, F, Chen K, Vieira, W, et al. Sorting of Pmel17 to melanosomes through the plasma membrane by AP1 and AP2: evidence for the polarized nature of melanocytes. J Cell Sci. 2006;119:1086–91.CrossRefGoogle Scholar
  18. 18.
    Medzhitov R, Janeway CJ. The toll receptor family and microbial recognition. Trends Microbiol. 2000;8(10):452–6.CrossRefGoogle Scholar
  19. 19.
    O’Neill L, Golenbock D, Bowie A. The history of toll-like receptors – redefining innate immunity. Nat Rev Immunol. 2013;13:453–6.CrossRefGoogle Scholar
  20. 20.
    Touhg D. Type I interferon as a link between innate and adaptive immunity through dendritic cell stimulation. Leuk Lymphoma. 2004;45(2):257–64.CrossRefGoogle Scholar
  21. 21.
    Beutler B. TLRs and innate immunity. Blood. 2009;113:1399–407.CrossRefGoogle Scholar
  22. 22.
    Boehm L, Klamp T, Groot M, Howard J. Cellular responses to interferon-γ. Annu Rev Immunol. 1997;197:749–95.CrossRefGoogle Scholar
  23. 23.
    Kishimoto T. Interleukin–6: from basic science to medicine—40 years in immunology. Annu Rev Immunol. 2005;23:1–21.CrossRefGoogle Scholar
  24. 24.
    Korn T, Bettelli E, Oukka M, Kuchroo V. IL–17 and Th17 cells. Annu Rev Immunol. 2009;27:485–517.CrossRefGoogle Scholar
  25. 25.
    Parrish-Novak J, Dillon S, Nelson A, Hammond A, Sprecher C, Gross J, et al. Interleukin 21 and its receptor are involved in NK cell expansion and regulation of lymphocyte function. Nature. 2000;408:57–63.CrossRefGoogle Scholar
  26. 26.
    Leonard W, Spolski R. Interleukin–21: a modulator of lymphoid proliferation, apoptosis and differentiation. Nat Rev Immunol. 2005;5(9):68–98.CrossRefGoogle Scholar
  27. 27.
    Wheelock E. Interferon-like virus-inhibitor induced in human leukocytes by phytohemagglutin. Science. 1965;149:310–1.CrossRefGoogle Scholar
  28. 28.
    Brown M, Hural J. Functions of IL-4 and control of its expression. Crit Rev Immunol. 1997;17:1–32.CrossRefGoogle Scholar
  29. 29.
    Corcoran M, Stetler-Stevenson W, Brown P, Wahl L. Interlukin-4 inhibition of prostaglandin E2 synthesis blocks interstitial collagenase and 92-kDa type IV collagenase/gelatinase production by human monocytes. J Biol Chem. 1992;267:515–9.Google Scholar
  30. 30.
    Lee J, Swisher S, Minehart E, Mc Bride W, Economou J. Interleukine-4 down-regulates interleukin-6 production in human peripheral blood mononuclear cells. J Leukocyt Biology. 1990;47:475–9.CrossRefGoogle Scholar
  31. 31.
    Beebe A, Cua D, de Waal Malefyt R. The role of interleukin–10 in autoimmune disease: systemic lupus erythematosus (SLE) and multiple sclerosis (MS). Cytokine Growth Factor Rev. 2001;13(4):403–12.Google Scholar
  32. 32.
    Ceponis P, Botelho F, Richards C, McKay D. Interleukins 4 and 13 increase intestinal epithelial permeability by a phosphatidylinositol 3-kinase pathway. Lack of evidence for STAT 6 involvement. J Biol Chem. 2000;275(37):29132–7.CrossRefGoogle Scholar
  33. 33.
    Calandra T, Bucala R. Macrophage migration inhibitory factor (MIF): a glucocorticoid counter-regulator within the immune system. Crit Rev Immunol. 1997;17(1):77–88.CrossRefGoogle Scholar
  34. 34.
    Wahl S. Transforming growth factor-beta: innately bipolar. Curr Opin Immunol. 2007;19(1):55–62.CrossRefGoogle Scholar
  35. 35.
    Gorelik L, Flavell R. Transforming growth factor-beta in T cell biology. Nat Rev Immunol. 2002;2(1):46–53.CrossRefGoogle Scholar
  36. 36.
    Abbas A, Lichtman A, Pillai S. Cellular and molecular immunology. 6th ed. Philadelphia: Saunders; 2010.Google Scholar
  37. 37.
    Gotschlish E. C-reactive protein. A historical overview. Ann NY Acd Sci. 1989;557:9–18.CrossRefGoogle Scholar
  38. 38.
    Du Clos T, Mold C. C-reactive protein: an activator of innate immunity and a modulator of adaptive immunity. Immunol Res. 2001;30:261–77.CrossRefGoogle Scholar
  39. 39.
    Agrawal A. CRP after 2004. Mol Immunol. 2005;42:927–30.CrossRefGoogle Scholar
  40. 40.
    Davalos D, Akassoglou K. Fibrinogen as a key regulator of inflammation in disease. Semin Immunopathol. 2012;34(1):43–62.CrossRefGoogle Scholar
  41. 41.
    Quaye I. Haptoglobin, inflammation and disease. Trans Roy Soc Trop Med Hyg. 2008;102:735–42.CrossRefGoogle Scholar
  42. 42.
    Arredouan M, Matthijs P, Van Hoeyveld E, Kasran A, Baumann H, Ceuppens J, et al. Haptoglobin directly affects T cells and suppresses T helper cell type 2 cytokine release. Immunology. 2003;108:144–51.CrossRefGoogle Scholar
  43. 43.
    Atkins E. Pathogenesis of fever. Physiol Rev. 1960;40:580–646.CrossRefGoogle Scholar
  44. 44.
    Beeson P. Temperature-elevating effect of a substance obtained from polymorphonuclear leucocytes. J Clin Invest. 1948;27(4):524.Google Scholar
  45. 45.
    Dinarello C. Infection, fever, and exogenous and endogenous pyrogens: some concepts have changed. J Endotoxin Res. 2004;10:210–22.Google Scholar
  46. 46.
    Bicego K, Barros R, Branco L. Physiology of temperature regulation: comparative aspects. Comp Biochem Physiol A Mol Integr Physiol. 2007;147(3):615–39.CrossRefGoogle Scholar
  47. 47.
    Li M, Sanjabi S, Flavel R. Transforming growth factor-beta controls development, homeostasis, and tolerance of T cells by regulatory T cell-dependent and -independent mechanisms. Immunity. 2006;25(3):455–71.CrossRefGoogle Scholar
  48. 48.
    Adams-Chapman I, Stoll B. Prevention of nosocomial infections in the neonatal intensive care unit. Curr Opin Pediatr. 2002;14(2):157–64.CrossRefGoogle Scholar
  49. 49.
    Deitch E. Bacterial translocation or lymphatic drainage of toxic products from the gut: what is important in human beings. Surgery. 2002;131(13):241–4.CrossRefGoogle Scholar
  50. 50.
    Sharma. Neonatal gut barrier and multiple organ failure: role of endotoxin and proinflammatory cytokines in sepsis and necrotizing enterocolitis. J Pediatr Surg. 2007;42:454–61.CrossRefGoogle Scholar
  51. 51.
    Funk C. Prostaglandins and leukotrienes: advances in eicosanoid biology. Science. 2001;294:1871–5.CrossRefGoogle Scholar
  52. 52.
    Ivanov A, Romanovsky A. Prostaglandin E2 as a mediator of fever: synthesis and catabolism. Front Biosci. 2004;9:1977–93.CrossRefGoogle Scholar
  53. 53.
    Saper C, Romanovsky A, Scammel T. Neural circuitry engaged by prostaglandins during the sickness syndrome. Nat Neurosci. 2012;15:1088–95.CrossRefGoogle Scholar
  54. 54.
    Walter F, Boulpaep E. Medical physiology: a cellular and molecular approach. Philadelphia: Saunders; 2003.Google Scholar
  55. 55.
    IUPS TC. Glossary of terms to thermal physiology. Pflugers Archives. 1987;410:567–87.CrossRefGoogle Scholar
  56. 56.
    Sund Levander M. Body temperature (Kroppstemperatur) In: Edberg AW, H Wijk, editors. The base for nursing care health and illness (Omvårdnadens grunder Hälsa och ohälsa) in Swedish. 3 ed. Lund: Studentlitteratur; 2014.Google Scholar

General Reference

  1. Murphy K. Janeway’s immunobiology. New York: Garland Science; 2016.CrossRefGoogle Scholar

Copyright information

© The Author(s) 2020

Authors and Affiliations

  • Ewa Grodzinsky
    • 1
  • Märta Sund Levander
    • 2
  1. 1.Department of Pharmaceutic ResearchLinköping UniversityLinköpingSweden
  2. 2.Department of NursingLinköping UniversityLinköpingSweden

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