Skip to main content
SpringerLink
Log in

Flu-Like Syndrome and Cytokines

  • Protocol
Cytokines in Human Health

Part of the book series: Methods in Pharmacology and Toxicology ((MIPT))

Abstract

Flu-like reactions have been described, long before the introduction of therapeutic cytokines, in the clinical setting to treat a variety of pathological conditions. Indeed, flu-like reactions are commonly associated with vaccination as well as a number of infectious diseases unrelated to the influenza virus. Flu-like symptoms have also been described after the early use of supposedly immunostimulating drugs. When the first interferon formulations began to be used to treat cancerous patients, flu-like symptoms with some variation according to the type of interferon, route of administration, schedule, and dose, were observed in most patients. Since then, the flu-like syndrome emerged as a common-if-not universal complication of therapeutic cytokines.

This is a preview of subscription content, log in via an institution to check access.

Access this chapter

Log in via an institution
Protocol
USD 49.95
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
eBook
USD 129.00
Price excludes VAT (USA)
  • Available as EPUB and PDF
  • Read on any device
  • Instant download
  • Own it forever
Softcover Book
USD 169.99
Price excludes VAT (USA)
  • Compact, lightweight edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info
Hardcover Book
USD 169.99
Price excludes VAT (USA)
  • Durable hardcover edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info

Tax calculation will be finalised at checkout

Purchases are for personal use only

Institutional subscriptions

References

  1. Zhou W, Pool V, Iskander JK, et al. Surveillance for safety after immunization: Vaccine Adverse Event Reporting System (VAERS) — United States, 1991–2001. MMWR Surveill Summ 2003;52:1–24.

    PubMed  Google Scholar 

  2. Descotes J. Adverse consequences of chemical immunomodulation. Clin Res Pract Drug Regul Affairs 1985;3:45–52.

    Article  Google Scholar 

  3. Quesada JR, Talpaz M, Rios A, Kurzrock R, Gutterman JU. Clinical toxicity of interferons in cancer patients: a review. J Clin Oncol 1986;4:234–243.

    CAS  PubMed  Google Scholar 

  4. Vial T, Descotes J. Immune-mediated side-effects of cytokines in humans. Toxicology 1995; 105:31–57.

    Article  CAS  PubMed  Google Scholar 

  5. Guieu JD, Hellon RF The chill sensation in fever. Pflugers Arch 1980;384: 103–104.

    Article  CAS  PubMed  Google Scholar 

  6. Baracos V, Rodemann HP, Dinarello CA, Goldberg AL. Stimulation of muscle protein degradation and prostaglandin E2 release by leukocytic pyrogen (interleukin-1). A mechanism for the increased degradation of muscle proteins during fever. N Engl J Med 1983;308:553–558.

    Article  CAS  PubMed  Google Scholar 

  7. Smith RS The cytokine theory of headache. Med Hypotheses 1992;39:168–174.

    Article  CAS  PubMed  Google Scholar 

  8. Gordon MS, Battiato LA, Gonin R, Harrison-Mann BC, Loehrer PJ. A phase II trial of subcutaneously administered recombinant human interleukin-2 in patients with relapsed/refractory thymoma. J. Immunother. Emphasis Tumor Immunol. 1995;18:179–184.

    CAS  PubMed  Google Scholar 

  9. Sleijfer S, Bannink M, Van Gool AR, Kruit WH, Stoter G. Side effects of interferon-alpha therapy. Pharm World Sci 2005;27:423–431.

    Article  CAS  PubMed  Google Scholar 

  10. Vial T, Descotes J. Clinical toxicity of the interferons. Drug Saf 1994; 10:115–159.

    Article  CAS  PubMed  Google Scholar 

  11. Pardo M, Marriott E, Moliner MC, Quiroga JA, Carreno V. Risks and benefits of interferon-alpha in the treatment of hepatitis. Drug Saf 1995;13:304–316.

    Article  CAS  PubMed  Google Scholar 

  12. Ascione A, De Luca M, Di Costanzo GG, et al. Incidence of side effects during therapy with different types of alpha interferon: a randomised controlled trial comparing recombinant alpha 2b versus leukocyte interferon in the therapy of naive patients with chronic hepatitis C. Curr Pharm Des 2002;8:977–980.

    Article  CAS  PubMed  Google Scholar 

  13. Laguno M, Murillas J, Blanco JL, et al. Peginterferon alfa-2b plus ribavirin compared with interferon alfa-2b plus ribavirin for treatment of HIV/HCV co-infected patients. AIDS 2004;18:F27–36

    Article  CAS  PubMed  Google Scholar 

  14. Festi D, Sandri L, Mazzella G, et al. Colecchia A Safety of interferon beta treatment for chronic HCV hepatitis. World J Gastroenterol 2004; 10:12–16.

    CAS  PubMed  Google Scholar 

  15. Weinstock-Guttman B, Rudick RA. Prescribing recommendations for interferon-beta in multiple sclerosis. CNS Drugs 1997;8:102–112.

    Article  CAS  Google Scholar 

  16. Falcone NP, Nappo A, Neuteboom B. Interferon beta-la overdose in a multiple sclerosis patient. Ann Pharmacother 2005;39:1950–1952.

    Article  PubMed  Google Scholar 

  17. Vlachoyiannopoulos PG, Tsifetaki N, Dimitriou I, Galaris D, Papiris SA, Moutsopoulos HM. Safety and efficacy of recombinant gamma interferon in the treatment of systemic sclerosis. Ann Rheum Dis 1996;55:761–768.

    Article  CAS  PubMed  Google Scholar 

  18. Veltri S, Smith JW. Interleukin 1 trials in cancer patients: a review of the toxicity, antitumor and hematopoietic effects. Stem Cells 1996; 14:164–176.

    Article  CAS  PubMed  Google Scholar 

  19. Vial T, Descotes J Clinical toxicity of interleukin-2. Drug Saf. 1992;7:417–433.

    Article  CAS  PubMed  Google Scholar 

  20. Atkins MB. Interleukin-2: clinical applications. Semin Oncol 2002;29:S 12–17.

    Article  CAS  PubMed  Google Scholar 

  21. Kohler PC, Hank JA, Moore KH, Storer B, Bechhofer R, Sondel PM. Phase 1 clinical evaluation of recombinant interleukin-2. Prog Clin Biol Res 1987;244: 161–172.

    CAS  PubMed  Google Scholar 

  22. Lopez-Jimenez J, Perez-Oteyza J, Munoz A, et al. Subcutaneous versus intravenous low-dose IL-2 therapy after autologous transplantation: results of a prospective, non-randomized study. Bone Marrow Transplant 1997; 19:429–434.

    Article  CAS  PubMed  Google Scholar 

  23. De Vries EG, Van Gameren MM, Willemse PH. Recombinant human interleukin 3 in clinical oncology. Stem Cells 1993; 11:72–80.

    Article  PubMed  Google Scholar 

  24. Majhail NS, Hussein M, Olencki TE, et al. Phase I trial of continuous infusion recombinant human interleukinin patients with cancer. Invest New Drugs 2004;22:421–426.

    Article  CAS  PubMed  Google Scholar 

  25. Weber J, Yang JC, Topalian SL, et al. Phase I trial of subcutaneous interleukin-6 in patients with advanced malignancies. J Clin Oncol 1993; 11:499–506.

    CAS  PubMed  Google Scholar 

  26. Sosman JA, Aronson FR, Sznol M, et al. Concurrent phase I trials of intravenous interleukin 6 in solid tumor patients: reversible dose-limiting neurological toxicity. Clin Cancer Res 1997;3:39–46.

    CAS  PubMed  Google Scholar 

  27. Fedorak RN, Gangl A, Elson CO, et al. Recombinant human interleukin 10 in the treatment of patients with mild to moderately active Crohn’s disease. The Interleukin 10 Inflammatory Bowel Disease Cooperative Study Group. Gastroenterology 2000; 119:1473–1482.

    CAS  Google Scholar 

  28. Smith JW. Tolerability and side-effect profile of rhIL-11. Oncology 2000; 14, S41–S47.

    Google Scholar 

  29. Zeuzem S, Hopf U, Carreno V, et al. A phase I/II study of recombinant human interleukin-12 in patients with chronic hepatitis C. Hepatology 1999;29:1280–1287.

    Article  CAS  PubMed  Google Scholar 

  30. Spriggs DR, Sherman ML, Frei E, Kufe DW. Clinical studies with tumour necrosis factor. Ciba Found Symp 1987;131:206–227.

    CAS  PubMed  Google Scholar 

  31. Rauthe G, Sistermanns J. Recombinant tumour necrosis factor in the local therapy of malignant pleural effusion. Eur J Cancer 1997;33:226–231.

    Article  CAS  PubMed  Google Scholar 

  32. Vial T, Descotes J. Clinical toxicity of cytokines used as haemopoietic growth factors. Drug Saf 1995;13:371–406.

    Article  CAS  PubMed  Google Scholar 

  33. Voravud N, Sriuranpong V. Clinical benefits of epoetin alfa (Eprex) 10,000 units subcutaneously thrice weekly in Thai cancer patients with anemia receiving chemotherapy. J Med Assoc Thai 2005;88:607–612.

    PubMed  Google Scholar 

  34. Sgro C Side-effects of a monoclonal antibody, muromonab CD3/orthoclone OKT3: bibliographic review. Toxicology 1995;105:23–29.

    Article  CAS  PubMed  Google Scholar 

  35. Dillman RO. Infusion reactions associated with the therapeutic use of monoclonal antibodies in the treatment of malignancy. Cancer Metastasis Rev 1999; 18:465–471.

    Article  CAS  PubMed  Google Scholar 

  36. Onrust SV, Lamb HM, Balfour JA. Rituximab. Drugs 1999;58:79–88.

    Article  CAS  PubMed  Google Scholar 

  37. McKeage K, Perry CM. Trastuzumab: a review of its use in the treatment of metastatic breast cancer overexpressing HER2. Drugs 2002;62:209–243.

    Article  CAS  PubMed  Google Scholar 

  38. Hanauer SB Safety of infliximab in clinical trials. Aliment Pharmacol Ther 1999;13:S16–S22.

    Article  Google Scholar 

  39. Thrush GR, Lark LR, Clinchy BC, Vitetta ES. Immunotoxins: an update. Annu Rev Immunol 1996; 14:49–71.

    Article  CAS  PubMed  Google Scholar 

  40. Fisher B, Rubin H, Sartiano G, Ennis L, Wolmark N. Observations following Corynebacterium parvum administration to patients with advanced malignancy, a phase I study. Cancer 1976;38:119–130.

    Article  CAS  PubMed  Google Scholar 

  41. Brodsky I, Strayer DR, Krueger LJ, Carter WA. Clinical studies with ampligen (mismatched double-stranded RNA). J. Biol. Response Mod 1985;4:669–675.

    CAS  PubMed  Google Scholar 

  42. Giantonio BJ, Hochster H, Blum R, et al. Toxicity and response evaluation of the interferon inducer poly ICLC administered at low dose in advanced renal carcinoma and relapsed or refractory lymphoma: a report of two clinical trials of the Eastern Cooperative Oncology Group. Invest. New Drugs 2001;19:89–92.

    Article  CAS  PubMed  Google Scholar 

  43. Scheinfeld N, Rosenberg JD, Weinberg JM Levamisole in dermatology: a review. Am J Clin Dermatol 2004;5:97–104.

    Article  PubMed  Google Scholar 

  44. Gupta AK, Browne M, Bluhm R. Imiquimod: a review. J Cutan Med Surg 2002;6:554–560.

    Article  PubMed  Google Scholar 

  45. Kazar J. Coxiella burnetii Infection. Ann NY Acad Sci 2005; 1063:105–114.

    Article  PubMed  Google Scholar 

  46. Williams J, Tallis G, Dalton C, et al. Community outbreak of psittacosis in a rural Australian town. Lancet 1998;351:1697–1699.

    Article  CAS  PubMed  Google Scholar 

  47. Straus DC, Cooley JD, Wong WC, Jumper CA. Studies on the role of fungi in Sick Building Syndrome. Arch Environ Health 2003;58:475–478.

    Article  PubMed  Google Scholar 

  48. Prins JB, Van der Meer JW, Bleijenberg G. Chronic fatigue syndrome. Lancet 2006;367:346–355.

    Article  PubMed  Google Scholar 

  49. Sinzinger H Flu-like response on statins. Med Sci Monit 2004;8:384–388.

    Google Scholar 

  50. Green MR. Gemcitabine safety overview. Semin Oncol 1996;23:S32–S35.

    Google Scholar 

  51. Body JJ, Diel I, Bell R. Profiling the safety and tolerability of bisphosphonates. Semin Oncol 2004;31:S73–S78.

    Article  Google Scholar 

  52. Santini D, Fratto ME, Vincenzi B, La Cesa A, Dianzani C, Tonini G. Bisphosphonate effects in cancer and inflammatory diseases: in vitro and in vivo modulation of cytokine activities. BioDrugs 2004; 18:269–278.

    Article  CAS  PubMed  Google Scholar 

  53. Bengtsson BO, Wiholm BE, Myrhed M, Walinder J. Adverse experiences during treatment with zimeldine on special licence in Sweden. Int Clin Psychopharmacol 1994;9:55–61.

    Article  CAS  PubMed  Google Scholar 

  54. Wernicke JF The side effect profile and safety of fluoxetine. J Clin Psychiatry 1985;46:59–67.

    CAS  PubMed  Google Scholar 

  55. Kim SW, Pentel PR. Flu-like symptoms associated with fluoxetine overdose: a case report. J Toxicol Clin Toxicol 1989;27:389–393.

    Article  CAS  PubMed  Google Scholar 

  56. Shrivastava RK, Itil TM. Flu-like illness after discontinuance of imipramine. Biol Psychiatry 1985;20:792–794.

    Article  CAS  PubMed  Google Scholar 

  57. Lejoyeux M, Rodiere-Rein C, Ades J. Withdrawal syndrome from antidepressive drugs. Report of 5 cases. Encephale 1992; 18:251–255.

    CAS  PubMed  Google Scholar 

  58. Rosenbaum JF, Zajecka J. Clinical management of antidepressant discontinuation. J. Clin Psychiatry 1997;58:S37–S40.

    Google Scholar 

  59. Farrel M Opiate withdrawal. Addiction 1994;89:1471–1475.

    Article  Google Scholar 

  60. Amsterdam JD, Garcia-Espana F, Rybakowski J. Rates of flu-like infection in patients with affective illness. J Affect Disord 1998;47:177–182.

    Article  CAS  PubMed  Google Scholar 

  61. Kuschner WG, D’Alessandro A, Wong H, Blanc PD. Early pulmonary cytokine responses to zinc oxide fume inhalation. Environ Res 1997;75:7–11.

    Article  CAS  PubMed  Google Scholar 

  62. Grace TW, Platt FW. Subacute carbon monoxide poisoning. Another great imitator. JAMA 1981;246:1698–1700.

    Article  CAS  PubMed  Google Scholar 

  63. Dolan MC, Haltom TL, Barrows GH, Short CS, Ferriell KM. Carboxyhemoglobin levels in patients with flu-like symptoms. Ann Emerg Med 1987; 16: 782–786.

    Article  CAS  PubMed  Google Scholar 

  64. Leikin JB, Heckerling P, Maturen A, Perkins JT, Hryhorczuk DO. Carboxyhemoglobin levels in patients with flu-like symptoms. Ann Emerg Med 1988; 17: 383–384.

    Article  CAS  PubMed  Google Scholar 

  65. Rio J, Nos C, Marzo ME, Tintore M, Montalban X. Low-dose steroids reduce flu-like symptoms at the initiation of IFNbeta-lb in relapsing-remitting MS. Neurology 1998;50:1910–1912.

    CAS  PubMed  Google Scholar 

  66. Rio J, Nos C, Bonaventura I, et al. Corticosteroids, ibuprofen, and acetaminophen for IFNbeta-la flu symptoms in MS: a randomized trial. Neurology 2004;63:525–528.

    CAS  PubMed  Google Scholar 

  67. Rees J, Haas J, Gabriel K, Fuhlrott A, Fiola M. Both paracetamol and ibuprofen are equally effective in managing flu-like symptoms in relapsing-remitting multiple sclerosis patients during interferon beta-la (AVONEX) therapy. Mult Scler 2002;8:15–18.

    Article  Google Scholar 

  68. Saper CB, Breder CD. The neurologic basis of fever. N Engl J Med 1994;330: 1880–1886.

    Article  CAS  PubMed  Google Scholar 

  69. Conti B, Tabarean I, Andrei C, Bartfai T. Cytokines and fever. Front Biosci 2004;9:1433–1449.

    Article  CAS  PubMed  Google Scholar 

  70. Banks WA, Kastin A. Blood to brain transport of interleukin links the immune and central nervous systems. Life Sci 1991;48: L117–L121.

    Article  Google Scholar 

  71. Dinarello CA, Gatti S, Bartfai T. Fever: links with an ancient receptor. Curr Biol, 1999;9:R147–R150.

    Article  CAS  PubMed  Google Scholar 

  72. Milton AS, Wendlandt S. Effect on body temperature of prostaglandins of the A, E, and F series on injection into the third ventricle of unanesthetized cats and rabbits J Physiol 1971;218:325–336.

    CAS  PubMed  Google Scholar 

  73. Cao C, Matsumura K, Yamagata K, Watanabe Y. Induction by lipopolysaccharide of cyclooxygenase-2 mRNA in rat brain; its possible role in the febrile response. Brain Res 1995;697:187–196.

    Article  CAS  PubMed  Google Scholar 

  74. Zeisberger E. From humoral fever to neuroimmunological control of fever. J Thermal Biol 1999;24:287–326.

    Article  CAS  Google Scholar 

  75. Romanovsky AA, Simons CT, Szekely M, Kulchitsky VA. The vagus nerve in the thermoregulatory response to systemic inflammation. Am J Physiol 1997;273:R407–R413.

    CAS  PubMed  Google Scholar 

  76. Blatteis CM, Li S, Li Z, Feleder C, Perlik V. Cytokines, PGE2 and endotoxic fever: a re-assessment. Prostag Other Lipid Mediat 2005;76:1–18.

    CAS  Google Scholar 

  77. Sehic E, Li S, Ungar AL, Blatteis CM. Complement reduction impairs the febrile response of guinea pigs to endotoxin. Am J Physiol 1998;274: R1594–R1603.

    CAS  PubMed  Google Scholar 

  78. Van der Kolk LE, Grillo-Lopez AJ, Baars JW, et al. Complement activation plays a key role in the side-effects of rituximab treatment. Br J Haematol 2001; 115:807–811.

    Article  PubMed  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Poison Center and Pharmacovigilance Unit, Claude Bernard University, Lyon Cedex 03, France

    Jacques Descotes & Thierry Vial

Authors
  1. Jacques Descotes
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Thierry Vial
    View author publications

    You can also search for this author in PubMed Google Scholar

Editor information

Editors and Affiliations

  1. DyPort Vaccine Company, LLC, Frederick, MD

    Robert V. House

  2. Poison Center and Pharmacovigilance Unit, Lyon Cedex, France

    Jacques Descotes

Rights and permissions

Reprints and permissions

Copyright information

© 2007 Humana Press Inc., Totowa, NJ

About this protocol

Cite this protocol

Descotes, J., Vial, T. (2007). Flu-Like Syndrome and Cytokines. In: House, R.V., Descotes, J. (eds) Cytokines in Human Health. Methods in Pharmacology and Toxicology. Humana Press. https://doi.org/10.1007/978-1-59745-350-9_10

Download citation

  • DOI: https://doi.org/10.1007/978-1-59745-350-9_10

  • Publisher Name: Humana Press

  • Print ISBN: 978-1-58829-467-8

  • Online ISBN: 978-1-59745-350-9

  • eBook Packages: Springer Protocols

Publish with us

Policies and ethics

Search

Navigation