Journal of Equine Veterinary Science
Volume 27, Issue 7 , Pages 307-312 , July 2007

The Effect of Cimetidine and Aminoguanidine on Pro-inflammatory Cytokines in the Horse

  • Robert P. Hunter, MS, PhD

      Affiliations

    • From the Departments of Veterinary Physiology, Pharmacology, and Toxicology
    • Corresponding Author InformationReprint requests: Robert P. Hunter, Elanco Animal Health, A Division of Eli Lilly and Company, 2001 West Main Street, Greenfield, IN 46140.
    • ,
  • Charles R. Short, DVM, PhD

      Affiliations

    • From the Departments of Veterinary Physiology, Pharmacology, and Toxicology
    • ,
  • Michael J. Myers, PhD

      Affiliations

    • Division of Animal Research, Center for Veterinary Medicine, Food & Drug Administration, Laurel, Maryland
    • ,
  • Dorothy E. Farrell, BS

      Affiliations

    • Division of Animal Research, Center for Veterinary Medicine, Food & Drug Administration, Laurel, Maryland
    • ,
  • James R. McClure, DVM

      Affiliations

    • Veterinary Clinical Science, School of Veterinary Medicine, Louisiana State University, Baton Rouge, Louisiana
    • ,
  • Catherine E. Koch, MS

      Affiliations

    • From the Departments of Veterinary Physiology, Pharmacology, and Toxicology
    • ,
  • Michael L. Keowen, BS

      Affiliations

    • From the Departments of Veterinary Physiology, Pharmacology, and Toxicology

References 

  1. Kubes P, Suzuki M, Granger DN. Nitric oxide: an endogenous modulator of leukocyte adhesion. Proc Natl Acad Sci USA. 1991;88:4651–4655
  2. Osborn L. Leukocyte adhesion to endothelium in inflammation. Cell. 1990;62:3–6
  3. Groeneveld PHP, Kwappenberg KMC, Langermans JAM, Nibbering PH, Curtis L. Relation between pro- and anti-inflammatory cytokines and the production of nitric oxide (NO) in severe sepsis. Cytokine. 1997;9:138–142
  4. Melchiorri C, Meliconi R, Frizziero L, Silvestri T, Pulsatelli L, Mazzetti I. Enhanced and coordinated in vivo expression of inflammatory cytokines and nitric oxide synthase by chondrocytes from patients with osteoarthritis. Arth Rheum. 1998;41:2165–2174
  5. May SA. Cytokines in the pathogenesis of equine joint disease. In:  Schijns VECJ,  Horzinek MC editor. Cytokines in veterinary medicine. New York: CAB International; 1997;p. 191–199
  6. Bueno AC, Seahorn TL, Cornick-Seahorn J, Horohov DW, Moore RM. Plasma and urine nitric oxide concentrations in horses given a low dose of endotoxin. Am J Vet Res. 1999;60:969–976
  7. Emau P, Giri SN, Anderson GA, Stott JL, Osburn BI. Function of prostaglandins, thromboxane A2, and histamine in hypersensitivity reaction to experimental bluetongue disease in calves. Am J Vet Res. 1984;45:1852–1857
  8. Anderson GA, Stott JL, Gershwin LJ, Osburn BI. Subclinical and clinical bluetongue disease in cattle: clinical, pathological and pathogenic considerations. In:  Barber TL,  Jochim MM,  Osburn BI editor. Bluetongue and related orbiviruses. New York: Alan R. Liss, Inc.; 1985;p. 103–107
  9. White WB, Ballow M. Modulation of suppressor-cell activity by cimetidine in patients with common variable hypogammaglobulinemia. N Engl J Med. 1985;312:198–202
  10. Canning PC, Hassfurther RL, Knoblock KF. Histamine receptor antagonists enhance the resistance of immunosuppressed calves to bacterial pneumonia. J Leukoc Biol. 1995;(Suppl):25
  11. Goetz TE, Boulton CH, Ogilvie GK. Clinical management of progressive multifocal benign and malignant melanomas of horses with oral cimetidine. In: Royer MG, ed. Proceedings 35th Annual Convention American Association of Equine Practitioners; 1990:431–438.
  12. Goetz TE, Ogilvie GK, Keegan KG, Johnson PJ. Cimetidine for treatment of melanomas in three horses. J Am Vet Med Assoc. 1990;196:449–452
  13. Jenkins WL. Chemotherapeutic agents affecting host cellular functions: antineoplastics and immunomodulators. In:  Brander GC,  Pugh DM,  Bywater RJ,  Jenkins WL editor. Veterinary applied pharmacology & therapeutics. 5th ed.. London: Baillière Tindall; 1991;p. 392–411
  14. Vannier E, Dinarello CA. Histamine enhances interleukin (IL)-1-induced IL-6 gene expression and protein synthesis via H2 receptors in peripheral blood mononuclear cells. J Biol Chem. 1994;269:9952–9956
  15. Ogden BE, Hill HR. Histamine regulates lymphocyte mitogenic responses through activation of specific H1 and H2 histamine receptors. Immunology. 1980;41:107–114
  16. Tasaka N, Mio M, Shimazawa M, Nakaya N. Histamine-induced production of interleukin-1α from murine bone marrow stromal cells and its inhibition by H2 blockers. Mol Pharmacol. 1993;43:365–371
  17. Vannier E, Dinarello CA. Histamine enhances interleukin (IL)-1-induced IL-1 gene expression and protein synthesis via H2 receptors in peripheral blood mononuclear cells comparison with IL-1 receptor antagonist. J Clin Invest. 1993;92:281–287
  18. Mor S, Nagler A, Barak V, Handzel ZT, Geller-Bernstein C, Fabian I. Histamine enhances granulocyte-macrophage colony-stimulating factor and interleukin-6 production by human peripheral blood mononuclear cells. J Leukoc Biol. 1995;58:445–450
  19. Griffiths MJD, Messent M, MacAllister RJ, Evans TW. Aminoguanidine selectively inhibits inducible nitric oxide synthase. Br J Pharmacol. 1993;110:963–968
  20. Misko TP, Moore WM, Kasten TP, Nickols GA, Corbett JA, Tilton RG, et al. Selective inhibition of the inducible nitric oxide synthase by aminoguanidine. Eur J Pharmacol. 1993;233:119–125
  21. Griffiths MJD, Messent M, Curzen NP, Evans TW. Aminoguanidine selectively decreases cyclic GMP levels produced by inducible nitric oxide synthase. Am J Respir Crit Care Med. 1995;152:1599–1604
  22. Laszlo F, Evans SM, Whittle BJR. Aminoguanidine inhibits both constitutive and inducible nitric oxide synthase isoforms in rat intestinal microvascular in vivo. Eur J Pharmacol. 1995;272:169–175
  23. Sewer MB, Morgan ET. Nitric oxide-independent suppression of P450 2C11 expression by interleukin-1 and endotoxin in primary rat hepatocytes. Biochem Pharmacol. 1997;54:729–737
  24. Hunter RP, Short CR, McClure JR, Koch CE, Keowen ML, VanSteenhouse JL, et al. Cimetidine inhibits nitric oxide associated nitrate production in a soft-tissue inflammation model in the horse. J Vet Pharmacol Therap. 1999;22:136–147
  25. In:  Stiles WR,  Nall DA,  Davila JC,  Brown SA,  Wolf AM,  Ruoff WW editor. Formulary of the Texas A&M University Texas Veterinary Medical Center Veterinary Teaching Hospital. 2nd ed.. College Station, TX: Texas A&M University; 1990;
  26. Sams RA, Gerken DF, Dyke TM, Reed SM, Ashcraft SM. Pharmacokinetics of intravenous and intragastric cimetidine in horses: I. Effects of intravenous cimetidine on pharmacokinetics of intravenous phenylbutazone. J Vet Pharmacol Ther. 1997;20:355–361
  27. Smyth GB, Duran S, Ravis W, Clark CR. Pharmacokinetic studies of cimetidine hydrochloride in adult horses. Equine Vet J. 1990;22:48–50
  28. Foote EF, Look ZM, Giles P, Keane WF, Halstenson CE. The pharmacokinetics of aminoguanidine in end-stage renal disease patients on hemodialysis. Am J Kidney Dis. 1995;25:420–425
  29. Bowman MA, Simell OG, Peck AB, Cornelius J, Luchetta R, Look Z, et al. Pharmacokinetics of aminoguanidine administration and effects on the diabetes frequency in nonobese diabetic mice. J Pharmacol Exp Ther. 1996;279:790–794
  30. Corbett JA, Tilton RG, Chang K, Hasan KS, Ido Y, Wang JL, et al. Aminoguanidine, a novel inhibitor of nitric oxide formation, prevents diabetic vascular dysfunction. Diabetes. 1992;41:552–556
  31. Schook LB, Lockwood JF, Yang S-D, Myers MJ. Dimethylnitrosamine (DMN)-induced IL-1β, TNF-α, and IL-6 inflammatory cytokine expression. Toxicol Appl Pharmacol. 1992;116:110–116
  32. Myers MJ, Farrell DE, Evock-Clover CM, Cope CV, Henderson M, Steele NC. Effect of recombinant growth hormone and chromium picolinate on cytokine production and growth performance in swine. Pathobiology. 1995;63:283–287
  33. Myers MJ, Farrell DE, Evock-Clover CM, McDonald MW, Steele NC. Effect of growth hormone or chromium picolinate on swine metabolism and inflammatory cytokine production after endotoxin challenge exposure. Am J Vet Res. 1997;58:594–600
  34. Gibaldi M, Perrier P. Pharmacokinetics. 2nd ed.. New York: Marcel Dekker; 1982;445−449
  35. Daniel WW. Applied nonparametric statistics. 2nd ed.. Boston, MA: PWS-Kent Publishing Company; 1990;262−277
  36. Hirasawa N, Watanabe M, Mue S, Tsurufuji S, Ohuchi K. Downward regulation of neutrophil infiltration by endogenous histamine without affecting vascular permeability responses in air-pouch-type carrageenin inflammation. Inflammation. 1991;15:117–126
  37. van de Loo FAJ, Kuiper S, van Enckevort FHJ, Arntz OJ, van den Berg WB. Interleukin-6 reduces cartilage destruction during experimental arthritis: a study in interleukin-6-deficient mice. Am J Pathol. 1997;151:177–191
  38. Richards CD, Scamurra RW, Murtaugh MP. Interleukin-6. In:  Myers MJ,  Murtaugh MP editor. Cytokines in animal health and disease. New York: Marcel Dekker, Inc.; 1995;p. 153–182
  39. Merétey K, Falus A, Taga T, Kishimoto T. Histamine influences the expression of the interleukin-6 receptor on human lymphoid, monocytoid and hepatoma cell lines. Agents Actions. 1991;33:189–191

PII: S0737-0806(07)00194-3

doi: 10.1016/j.jevs.2007.05.007

Journal of Equine Veterinary Science
Volume 27, Issue 7 , Pages 307-312 , July 2007

Article Tools

* Image Usage & Resolution