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Fundamentals of Clinical Immunotoxicology

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Immunotoxicity Testing

Part of the book series: Methods in Molecular Biology™ ((MIMB,volume 598))

Abstract

Whereas animal studies are invaluable for screening various chemical and drugs for immunotoxic potential, such systems are necessarily limited in their predictive value for humans given the differences in physiology, immune system structure and function, and various other parameters between humans and nonhuman animals. However, prospective experimental studies in humans are not always practical or ethical. What is needed is an approach for combining animal data, human data collected in the course of clinical studies, and modern tools of bioinformatics and systems biology. In this chapter, we will explore current assays and methodologies for assessing immunotoxic potential in humans using this multi-­parameter approach.

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References

  1. House RV, Hastings KL (2004) Multidimen-sional immunomodulation. J Immunotoxicol 1:123–129

    Article  PubMed  Google Scholar 

  2. Gregson AL, Edelman R (2003) Does antigenic overload exist? The role of multiple immunizations in infants. Immunol Allergy Clin North Am 23(4):649–664

    Article  PubMed  Google Scholar 

  3. Offit PA, Quarles J, Gerber MA, Hackett CJ, Marcuse EK, Kollman TR, Gellin BG, Landry S (2002) Addressing parents’ concerns: do multiple vaccines overwhelm or weaken the infant’s immune system? Pediatrics 109(1):124–129

    Article  PubMed  Google Scholar 

  4. Offit PA, Hackett CJ (2003) Addressing parents’ concerns: do vaccines cause allergic or autoimmune diseases? Pediatrics 111(3):653–659

    Article  PubMed  Google Scholar 

  5. Schattner A (2005) Consequence or coincidence? The occurrence, pathogenesis and significance of autoimmune manifestations after viral vaccines. Vaccine 23(30):3876–3886

    Article  CAS  PubMed  Google Scholar 

  6. Goriely S, Goldman M (2007) From tolerance to autoimmunity: is there a risk in early life vaccination? J Comp Pathol 137(Suppl 1):S57–S61

    Article  CAS  PubMed  Google Scholar 

  7. Siegrist CA (2007) Mechanisms underlying adverse reactions to vaccines. J Comp Pathol 137(Suppl 1):S46–S50

    Article  CAS  PubMed  Google Scholar 

  8. Garn H, Renz H (2007) Epidemiological and immunological evidence for the hygiene hypothesis. Immunobiology 212(6):441–452

    Article  CAS  PubMed  Google Scholar 

  9. Ramsey CD, Celedón JC (2005) The hygiene hypothesis and asthma. Curr Opin Pulm Med 11(1):14–20

    Article  PubMed  Google Scholar 

  10. Sánchez-Solis M, García-Marcos L (2006) Do vaccines modify the prevalence of asthma and allergies? Expert Rev Vaccines 5(5):631–640

    Article  PubMed  Google Scholar 

  11. Taylor B (2006) Vaccines and the changing epidemiology of autism. Child Care Health Dev 32(5):511–519

    Article  CAS  PubMed  Google Scholar 

  12. Offit PA, Coffin SE (2003) Communicating science to the public: MMR vaccine and autism. Vaccine 22(1):1–6

    Article  PubMed  Google Scholar 

  13. Parker SK, Schwartz B, Todd J, Pickering LK (2004) Thimerosal-containing vaccines and autistic spectrum disorder: a critical review of published original data. Pediatrics 114(3):793–804

    Article  PubMed  Google Scholar 

  14. DeStefano F (2007) Vaccines and autism: evidence does not support a causal association. Clin Pharmacol Ther 82(6):756–759

    Article  CAS  PubMed  Google Scholar 

  15. Dietert RR, Dietert JM (2008) Potential for early-life immune insult including developmental immunotoxicity in autism and autism spectrum disorders: focus on critical windows of immune vulnerability. J Toxicol Environ Health B Crit Rev 11(8):660–680

    CAS  PubMed  Google Scholar 

  16. House RV, Luebke RW (2006) Immuno-toxicology: thirty years and counting. In: Luebke R, House R, Kimber I (eds) Immunopharmacology and immunotoxicology, 3rd edn. CRC, Boca Raton, pp 3–20

    Google Scholar 

  17. Ponce R (2008) Adverse consequences of immunostimulation. J Immunotoxicol 5(1):33–41

    Article  CAS  PubMed  Google Scholar 

  18. Suntharalingam G, Perry MR, Ward S, Brett SJ, Castello-Cortes A, Brunner MD, Panoskaltsis N (2006) Cytokine storm in a phase 1 trial of the anti-CD28 monoclonal antibody TGN1412. N Engl J Med 355:1018–1028

    Article  CAS  PubMed  Google Scholar 

  19. Wang H, Ma S (2008) The cytokine storm and factors determining the sequence and severity of organ dysfunction in multiple organ dysfunction syndrome. Am J Emerg Med 26(6):711–715

    Article  PubMed  Google Scholar 

  20. Stebbings R, Findlay L, Edwards C, Eastwood D, Bird C, North D, Mistry Y, Dilger P, Liefooghe E, Cludts I, Fox B, Tarrant G, Robinson J, Meager T, Dolman C, Thorpe SJ, Bristow A, Wadhwa M, Thorpe R, Poole S (2007) “Cytokine storm” in the phase I trial of monoclonal antibody TGN1412: better understanding the causes to improve preclinical testing of immunotherapeutics. J Immunol 179:3325–3331

    CAS  PubMed  Google Scholar 

  21. St. Clair EW (2008) The calm after the storm: lessons from the TGN1412 trial. J Clin Invest 118(4):1344–1347

    Google Scholar 

  22. Descotes J, Gouraud A (2008) Clinical immunotoxicity of therapeutic proteins. Expert Opin Drug Metab Toxicol 4(12):1537–1549

    Article  CAS  PubMed  Google Scholar 

  23. Luebke RW, Chen DH, Dietert R, Yang Y, King M, Luster MI, Immunotoxicology Workgroup (2006) The comparative immunotoxicity of five selected compounds following developmental or adult exposure. J Toxicol Environ Health B Crit Rev 9(1):1–26

    Article  CAS  PubMed  Google Scholar 

  24. Burns-Naas LA, Hastings KL, Ladics GS, Makris SL, Parker GA, Holsapple MP (2008) What’s so special about the developing immune system? Int J Toxicol 27(2):223–254

    Article  PubMed  Google Scholar 

  25. Luster MI, Johnson VJ, Yucesoy B, Simeonova PP (2005) Biomarkers to assess potential developmental immunotoxicity in children. Toxicol Appl Pharmacol 206(2):229–236

    Article  CAS  PubMed  Google Scholar 

  26. Dietert RR (2008) Developmental immunotoxicity (DIT) in drug safety testing: matching DIT testing to adverse outcomes and childhood disease risk. Curr Drug Saf 3(3):216–226

    Article  PubMed  Google Scholar 

  27. Dietert RR, Zelikoff JT (2008) Early-life environment, developmental immunotoxicology, and the risk of pediatric allergic disease including asthma. Birth Defects Res B Dev Reprod Toxicol 83(6):547–560

    Article  CAS  PubMed  Google Scholar 

  28. Phillips TM (2000) Assessing environmental exposure in children: immunotoxicology screening. J Expo Anal Environ Epidemiol 10(6 Pt 2):769–775

    Article  CAS  PubMed  Google Scholar 

  29. Heilmann C, Grandjean P, Weihe P, Nielsen F, Budtz-Jørgensen E (2006) Reduced antibody responses to vaccinations in children exposed to polychlorinated biphenyls. PLoS Med 3(8):e311

    Article  PubMed  Google Scholar 

  30. Soto-Peña GA, Luna AL, Acosta-Saavedra L, Conde P, López-Carrillo L, Cebrián ME, Bastida M, Calderón-Aranda ES, Vega L (2006) Assessment of lymphocyte subpopulations and cytokine secretion in children exposed to arsenic. FASEB J 20(6):779–781

    PubMed  Google Scholar 

  31. Duramad P, Tager IB, Holland NT (2007) Cytokines and other immunological biomarkers in children’s environmental health studies. Toxicol Lett 172(1–2):48–59

    Article  CAS  PubMed  Google Scholar 

  32. Dean JH, House RV, Luster MI (2007) Immunotoxicology: Effects of, and response to, drugs and chemicals. In: Hayes AW (ed) Principles and methods of toxicology, 5th edn. CRC, Boca Raton, pp 1755–1796

    Google Scholar 

  33. Evans E (2008) Clinical pathology as crucial insight into immunotoxicity testing. In: Herzyk DJ, Bussiere JL (eds) Immunotoxicology strategies for pharmaceutical safety assessment. Wiley, Hoboken, NJ, pp 13–26

    Google Scholar 

  34. Burns-Naas LA, Kerkvliet NI, Laskin DL, Bortner CD, Burchiel SW (2007) The use of multifunctional flow cytometry in immunotoxicology and immunopharmacology. In: Luebke R, House R, Kimber I (eds) Immunotoxicology and immunopharmacology, 3rd edn. CRC, Boca Raton, pp 97–122

    Google Scholar 

  35. Szczepański T, van der Velden VH, van Dongen JJ (2006) Flow-cytometric immunophenotyping of normal and malignant lymphocytes. Clin Chem Lab Med 44(7):775–796

    Article  PubMed  Google Scholar 

  36. Iciek L (2008) Evaluation of drug effects on immune cell phenotypes. In: Herzyk DJ, Bussiere JL (eds) Immunotoxicology strategies for pharmaceutical safety assessment. Wiley, Hoboken, NJ, pp 103–123

    Chapter  Google Scholar 

  37. Narayanan P, Capocasale RJ, Li N, Bugelski PJ (2008) Application of flow cytometery in drug development. In: Herzyk DJ, Bussiere JL (eds) Immunotoxicology strategies for pharmaceutical safety assessment. Wiley, Hoboken, NJ, pp 141–159

    Chapter  Google Scholar 

  38. Ladics GS (2007) Primary immune response to sheep red blood cells (SRBC) as the conventional T-cell dependent antibody response (TDAR) test. J Immunotoxicol 4(2):149–152

    Article  PubMed  Google Scholar 

  39. Bugelski PJ, Kim C (2007) T-dependent antigen response (TDAR) tests: meta-analysis of results generated across multiple laboratories. J Immunotoxicol 4(2):159–164

    Article  CAS  PubMed  Google Scholar 

  40. Van Loveren H, Van Amsterdam JG, Vandebriel RJ, Kimman TG, Rümke HC, Steerenberg PS, Vos JG (2001) Vaccine-induced antibody responses as parameters of the influence of endogenous and environmental factors. Environ Health Perspect 109(8):757–764

    Article  PubMed  Google Scholar 

  41. Sleijffers A, Kammeyer A, de Gruijl FR, Boland GJ, van Hattum J, van Vloten WA, van Loveren H, Teunissen MB, Garssen J (2003) Epidermal cis-urocanic acid levels correlate with lower specific cellular immune responses after hepatitis B vaccination of ultraviolet B-exposed humans. Photochem Photobiol 77(3):271–275

    Article  CAS  PubMed  Google Scholar 

  42. Colosio C, Fustinoni S, Corsini E, Bosetti C, Birindelli S, Boers D, Campo L, La Vecchia C, Liesivuori J, Pennanen S, Vergieva T, Van Amelsvoort LG, Steerenberg P, Swaen GM, Zaikov C, Van Loveren H (2007) Changes in serum markers indicative of health effects in vineyard workers following exposure to the fungicide mancozeb: an Italian study. Biomarkers 12(6):574–588

    Article  CAS  PubMed  Google Scholar 

  43. Baranska M, Van Amelsvoort L, Birindelli S, Fustinoni S, Corsini E, Liesivuori J, Van Loveren H (2008) Association of pesticide exposure, vaccination response, and interleukin-1 gene polymorphisms. Hum Exp Toxicol 27(9):709–713

    Article  CAS  PubMed  Google Scholar 

  44. Steerenberg P, van Amelsvoort L, Colosio C, Corsini E, Fustinoni S, Vergieva T, Zaikov C, Pennanen S, Liesivuori J, Van Loveren H (2008) Toxicological evaluation of the immune function of pesticide workers, a European wide assessment. Hum Exp Toxicol 27(9):701–707

    Article  CAS  PubMed  Google Scholar 

  45. House RV, Descotes J (eds) (2007) Cytokines in human health: immunotoxicology, pathology and clinical applications. Humana, Totawa, pp 366

    Google Scholar 

  46. Wong CK, Lam CW (2003) Clinical applications of cytokine assays. Adv Clin Chem 37:1–46

    Article  CAS  PubMed  Google Scholar 

  47. House RV (1999) Theory and practice of cytokine assessment in immunotoxicology. Methods 19(1):17–27

    Article  CAS  PubMed  Google Scholar 

  48. Gore E (2008) Functional cellular responses and cytokine profiles. In: Herzyk DJ, Bussiere JL (eds) Immunotoxicology strategies for pharmaceutical safety assessment. Wiley, Hoboken, NJ, pp 127–140

    Google Scholar 

  49. Ringerike T, Ullerås E, Völker R, Verlaan B, Eikeset A, Trzaska D, Adamczewska V, Olszewski M, Walczak-Drzewiecka A, Arkusz J, van Loveren H, Nilsson G, Lovik M, Dastych J, Vandebriel RJ (2005) Detection of immunotoxicity using T-cell based cytokine reporter cell lines (“Cell Chip”). Toxicology 206(2):257–272

    Article  CAS  PubMed  Google Scholar 

  50. Wagner W, Walczak-Drzewiecka A, Slusarczyk A, Biecek P, Rychlewski L, Dastych J (2006) Fluorescent Cell Chip a new in vitro approach for immunotoxicity screening. Toxicol Lett 162(1):55–70

    Article  CAS  PubMed  Google Scholar 

  51. Caligiuri MA (2008) Human natural killer cells. Blood 112(3):461–469

    Article  CAS  PubMed  Google Scholar 

  52. Moretta A, Locatelli F, Moretta L (2008) Human NK cells: from HLA class I-specific killer Ig-like receptors to the therapy of acute leukemias. Immunol Rev 224:58–69

    Article  CAS  PubMed  Google Scholar 

  53. House RV (1997) Immunotoxicology methods. In: Massaro, EJ (ed) Handbook of Human Toxicology, CRC, Boca Raton, FL, pp 677–708

    Google Scholar 

  54. Cederbrant K, Marcusson-Ståhl M, Condevaux F, Descotes J (2003) NK-cell activity in immunotoxicity drug evaluation. Toxicology 185(3):241–250

    Article  CAS  PubMed  Google Scholar 

  55. Plitnick L (2008) Natural killer cell assay and other innate immunity tests. In: Herzyk DJ, Bussiere JL (eds) Immunotoxicology strategies for pharmaceutical safety assessment. Wiley, Hoboken, NJ, pp 77–85

    Chapter  Google Scholar 

  56. Bilitewski U (2008) Determination of immunomodulatory effects: focus on functional analysis of phagocytes as representatives of the innate immune system. Anal Bioanal Chem 391(5):1545–1554

    Article  CAS  PubMed  Google Scholar 

  57. Bizzaro N (2007) Autoantibodies as predictors of disease: the clinical and experimental evidence. Autoimmun Rev 6(6):325–333

    Article  CAS  PubMed  Google Scholar 

  58. Tonutti E, Visentini D, Bizzaro N (2007) Interpretative comments on autoantibody tests. Autoimmun Rev 6(6):341–346

    Article  CAS  PubMed  Google Scholar 

  59. Nichols JE, Cortiella J, Lee J, Niles JA, Cuddihy M, Wang S, Bielitzki J, Cantu A, Mlcak R, Valdivia E, Yancy R, McClure ML, Kotov NA (2008) In vitro analog of human bone marrow from 3D scaffolds with biomimetic inverted colloidal crystal geometry. Biomaterials 30(6):1071–1079

    Google Scholar 

  60. Schanen BC, Drake DR III (2008) A novel approach for the generation of human dendritic cells from blood monocytes in the absence of exogenous factors. J Immunol Methods 335:53–64

    Article  CAS  PubMed  Google Scholar 

  61. Pollock PL, Germolec DR, Comment CE, Rosenthal GJ, Luster MI (1994) Development of human lymphocyte-engrafted SCID mice as a model for immunotoxicity assessment. Fundam Appl Toxicol 22(1):130–138

    Article  CAS  PubMed  Google Scholar 

  62. De Heer C, Schuurman HJ, Houben GF, Pieters RH, Penninks AH, van Loveren H (1995) The SCID-hu mouse as a tool in immunotoxicological risk assessment: effects of 2-acetyl-4(5)-tetrahydroxybutyl-imidazole (THI) and di-n-butyltin dichloride (DBTC) on the human thymus in SCID-hu mice. Toxicology 100(1–3):203–211

    PubMed  Google Scholar 

  63. Bugelski PJ (2005) Transgenic animals. In: Vohr H-W (ed) Encyclopedic reference of immunotoxicology. Springer, Berlin, pp 663–665

    Chapter  Google Scholar 

  64. House RV (2005) Transgenic rodent models in immunotoxicology. In: Tryphonas H, Fournier M, Blakley B, Smits J, Brousseau P (eds) Investigative immunotoxicology. CRC, Boca Raton, pp 345–362

    Chapter  Google Scholar 

  65. Løvik M (1997) Mutant and transgenic mice in immunotoxicology: an introduction. Toxicology 119(1):65–76

    Article  PubMed  Google Scholar 

  66. Davies MN, Flower DR (2007) Harnessing bioinformatics to discover new vaccines. Drug Discov Today 12(9/10):389–395

    Article  CAS  PubMed  Google Scholar 

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  1. DynPort Vaccine Company LLC, Frederick, MD, USA

    Robert V. House

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  1. Robert V. House
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Correspondence to Robert V. House .

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  1. College of Veterinary Medicine, Cornell University, Ithaca, 14853, U.S.A.

    Rodney R. Dietert

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House, R.V. (2010). Fundamentals of Clinical Immunotoxicology. In: Dietert, R. (eds) Immunotoxicity Testing. Methods in Molecular Biology™, vol 598. Humana Press. https://doi.org/10.1007/978-1-60761-401-2_24

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  • DOI: https://doi.org/10.1007/978-1-60761-401-2_24

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