FREE SHIPPING over $40
OVER 9000 FIVE-STAR REVIEWS
5% OFF ALL SUBSCRIPTIONS
100% HAPPINESS GUARANTEE
Analyze Diet
0
Home / Equine Research Bank / J Vet Intern Med / Effect of the p38 MAPK inhibitor doramapimod on the systemic...
Journal of veterinary internal medicine2020; 34(5); 2109-2116; doi: 10.1111/jvim.15847

Effect of the p38 MAPK inhibitor doramapimod on the systemic inflammatory response to intravenous lipopolysaccharide in horses.

Abstract: Doramapimod, a p38 MAPK inhibitor, is a potent anti-inflammatory drug that decreases inflammatory cytokine production in equine whole blood in vitro. It may have benefits for treating systemic inflammation in horses. Objective: To determine whether doramapimod is well tolerated when administered IV to horses, and whether it has anti-inflammatory effects in horses in a low-dose endotoxemia model. Methods: Six Standardbred horses. Methods: Tolerability study, followed by a blinded, randomized, placebo-controlled cross-over study. Horses were given doramapimod, and clinical and clinicopathological variables were monitored for 24 hours. Horses then were treated with doramapimod or placebo, followed by a low dose infusion of lipopolysaccharide (LPS). Clinical variables (heart rate, rectal temperature, noninvasive blood pressure), leukocyte count and tumor necrosis factor alpha (TNF-α) and interleukin-1 beta (IL-1β) concentrations were measured at multiple time points until 6 hours post-LPS infusion. Results: No adverse effects or clinicopathological changes were seen in the safety study. When treated with doramapimod as compared to placebo, horses had significantly lower heart rates (P = .03), rectal temperatures (P = .03), and cytokine concentrations (P = .03 for TNF-α and IL-1β), and a significantly higher white blood cell count (P = .03) after LPS infusion. Conclusions: Doramapimod has clinically relevant anti-inflammatory effects in horses, likely mediated by a decrease in leukocyte activation and decrease in the release of pro-inflammatory cytokines. To evaluate its potential as a novel treatment for systemic inflammatory response syndrome in horses, clinical trials will be necessary to determine its efficacy in naturally occurring disease.
© 2020 The Authors. Journal of Veterinary Internal Medicine published by Wiley Periodicals LLC. on behalf of the American College of Veterinary Internal Medicine.
Get Full Text
Publication Date: 2020-07-23 PubMed ID: 32700419PubMed Central: PMC7517855DOI: 10.1111/jvim.15847Google Scholar: Lookup
The Equine Research Bank provides access to a large database of publicly available scientific literature. Inclusion in the Research Bank does not imply endorsement of study methods or findings by Mad Barn.
LinkedInCopy
  • Journal Article
  • Randomized Controlled Trial
  • Veterinary

Summary

This research summary has been generated with artificial intelligence and may contain errors and omissions. Refer to the original study to confirm details provided. Submit correction.

The study investigates the effects of the drug doramapimod on the body’s inflammatory response in horses when given lipopolysaccharides (LPS). The researchers found that the drug, which inhibits a protein known to cause inflammation, has no adverse effects, lowers heart rate and temperature, reduces levels of pro-inflammatory factors and increases white blood cell count in horses, suggesting it could be beneficial for treating systemic inflammation in horses.

Research Objectives and Methods

  • The primary objective of the research was to determine the effects and tolerability of the drug, doramapimod, when given intravenously to horses. Another key aim was to inspect its anti-inflammatory influences in horses.
  • The experimental design was a two-part study, first focusing on the tolerability of the drug, followed by a blinded, randomized, placebo-controlled cross-over study.
  • For the experiments, six Standardbred horses were initially given doramapimod and monitored for 24 hours. Post this, they were either treated with doramapimod or a placebo before receiving a low dose of LPS. Basic vital signs, white blood cell count and certain protein levels were measured up to six hours after the LPS was administered.

Results of the Study

  • The study found no detected adverse effects or clinicopathological changes correlated with doramapimod in horses.
  • When horses were treated with doramapimod, compared to a placebo, it was found that they displayed lower heart rates, rectal temperatures, and pro-inflammatory cytokine concentrations. Doramapimod also led to an increased white blood cell count post LPS administration.

Conclusion and Future Implications

  • The research concludes that doramapimod has clinically relevant anti-inflammatory effects on horses, which are likely attributed to a decrease in the activation of white blood cells and the reduced release of pro-inflammatory proteins.
  • The significance of these findings underscores the potential of doramapimod as a novel treatment for systemic inflammatory response syndrome (a severe body-wide inflammatory state) in horses. However, clinical trials would be needed to assess its efficacy in treating naturally occurring diseases.

Cite This Article

APA
Bauquier J, Tudor E, Bailey S. (2020). Effect of the p38 MAPK inhibitor doramapimod on the systemic inflammatory response to intravenous lipopolysaccharide in horses. J Vet Intern Med, 34(5), 2109-2116. https://doi.org/10.1111/jvim.15847

Publication

Journal of veterinary internal medicine
ISSN: 1939-1676
NlmUniqueID: 8708660
Country: United States
Language: English
Volume: 34
Issue: 5
Pages: 2109-2116

Researcher Affiliations

Bauquier, Jennifer
  • Department of Veterinary Clinical Sciences, Melbourne Veterinary School, Faculty of Veterinary and Agricultural Sciences, University of Melbourne, Werribee, Victoria, Australia.
Tudor, Elizabeth
  • Department of Veterinary Biosciences, Melbourne Veterinary School, Faculty of Veterinary and Agricultural Sciences, University of Melbourne, Parkville, Australia.
Bailey, Simon
  • Department of Veterinary Biosciences, Melbourne Veterinary School, Faculty of Veterinary and Agricultural Sciences, University of Melbourne, Parkville, Australia.

MeSH Terms

  • Animals
  • Cross-Over Studies
  • Horse Diseases / drug therapy
  • Horses
  • Lipopolysaccharides
  • Naphthalenes
  • Pyrazoles
  • Systemic Inflammatory Response Syndrome / drug therapy
  • Systemic Inflammatory Response Syndrome / veterinary
  • Tumor Necrosis Factor-alpha
  • p38 Mitogen-Activated Protein Kinases

Conflict of Interest Statement

This compound is the subject of a patent application filed by the University of Melbourne (Patent number PCT/AU2018/050120, filed 15 Feb 2018).

References

This article includes 57 references
  1. Werners AH, Bull S, Fink-Gremmels J. Endotoxaemia: a review with implications for the horse.. Equine Vet J 2005 Jul;37(4):371-83.
    pubmed: 16028631doi: 10.2746/0425164054529418google scholar: lookup
  2. Lewis DH, Chan DL, Pinheiro D, Armitage-Chan E, Garden OA. The immunopathology of sepsis: pathogen recognition, systemic inflammation, the compensatory anti-inflammatory response, and regulatory T cells.. J Vet Intern Med 2012 May-Jun;26(3):457-82.
    pmc: PMC7166777pubmed: 22428780doi: 10.1111/j.1939-1676.2012.00905.xgoogle scholar: lookup
  3. Moore JN, Vandenplas ML. Is it the systemic inflammatory response syndrome or endotoxemia in horses with colic?. Vet Clin North Am Equine Pract 2014 Aug;30(2):337-51, vii-viii.
    pubmed: 25016495doi: 10.1016/j.cveq.2014.04.003google scholar: lookup
  4. Cohen ND, Woods AM. Characteristics and risk factors for failure of horses with acute diarrhea to survive: 122 cases (1990-1996).. J Am Vet Med Assoc 1999 Feb 1;214(3):382-90.
    pubmed: 10023402
  5. Orsini JA, Parsons CS, Capewell L, Smith G. Prognostic indicators of poor outcome in horses with laminitis at a tertiary care hospital.. Can Vet J 2010 Jun;51(6):623-8.
    pmc: PMC2871359pubmed: 20808574
  6. Traub-Dargatz JL, Kopral CA, Seitzinger AH, Garber LP, Forde K, White NA. Estimate of the national incidence of and operation-level risk factors for colic among horses in the United States, spring 1998 to spring 1999.. J Am Vet Med Assoc 2001 Jul 1;219(1):67-71.
    pubmed: 11439773doi: 10.2460/javma.2001.219.67google scholar: lookup
  7. Baskett A, Barton MH, Norton N, Anders B, Moore JN. Effect of pentoxifylline, flunixin meglumine, and their combination on a model of endotoxemia in horses.. Am J Vet Res 1997 Nov;58(11):1291-9.
    pubmed: 9361895
  8. Campbell NB, Blikslager AT. The role of cyclooxygenase inhibitors in repair of ischaemic-injured jejunal mucosa in the horse.. Equine Vet J Suppl 2000 Jun;(32):59-64.
    pubmed: 11202384doi: 10.1111/j.2042-3306.2000.tb05335.xgoogle scholar: lookup
  9. Forbes G, Bailey SR, Church S. Effects of flunixin meglumine on leukocyte activation in a low‐dose endotoxemia model in horses.. J Vet Int Med 2009;23:784‐785.
  10. Forbes G, Church S, Savage CJ, Bailey SR. Effects of hyperimmune equine plasma on clinical and cellular responses in a low-dose endotoxaemia model in horses.. Res Vet Sci 2012 Feb;92(1):40-4.
    pubmed: 21093001doi: 10.1016/j.rvsc.2010.10.020google scholar: lookup
  11. Kelmer G. Update on treatments for endotoxemia.. Vet Clin North Am Equine Pract 2009 Aug;25(2):259-70.
    pubmed: 19580938doi: 10.1016/j.cveq.2009.04.012google scholar: lookup
  12. Lees P, Higgins AJ. Clinical pharmacology and therapeutic uses of non-steroidal anti-inflammatory drugs in the horse.. Equine Vet J 1985 Mar;17(2):83-96.
    pubmed: 3987667doi: 10.1111/j.2042-3306.1985.tb02056.xgoogle scholar: lookup
  13. Marshall JF, Blikslager AT. The effect of nonsteroidal anti-inflammatory drugs on the equine intestine.. Equine Vet J Suppl 2011 Aug;(39):140-4.
    pubmed: 21790769doi: 10.1111/j.2042-3306.2011.00398.xgoogle scholar: lookup
  14. Spier SJ, Lavoie JP, Cullor JS, Smith BP, Snyder JR, Sischo WM. Protection against clinical endotoxemia in horses by using plasma containing antibody to an Rc mutant E. coli (J5).. Circ Shock 1989 Jul;28(3):235-48.
    pubmed: 2670308
  15. Ward A, Clissold SP. Pentoxifylline. A review of its pharmacodynamic and pharmacokinetic properties, and its therapeutic efficacy.. Drugs 1987 Jul;34(1):50-97.
    pubmed: 3308412doi: 10.2165/00003495-198734010-00003google scholar: lookup
  16. Brooks AC, Menzies-Gow NJ, Wheeler-Jones C, Bailey SR, Cunningham FM, Elliott J. Endotoxin-induced activation of equine platelets: evidence for direct activation of p38 MAPK pathways and vasoactive mediator production.. Inflamm Res 2007 Apr;56(4):154-61.
    pubmed: 17522813doi: 10.1007/s00011-006-6151-6google scholar: lookup
  17. Kumar S, Boehm J, Lee JC. p38 MAP kinases: key signalling molecules as therapeutic targets for inflammatory diseases.. Nat Rev Drug Discov 2003 Sep;2(9):717-26.
    pubmed: 12951578doi: 10.1038/nrd1177google scholar: lookup
  18. Pargellis C, Tong L, Churchill L, Cirillo PF, Gilmore T, Graham AG, Grob PM, Hickey ER, Moss N, Pav S, Regan J. Inhibition of p38 MAP kinase by utilizing a novel allosteric binding site.. Nat Struct Biol 2002 Apr;9(4):268-72.
    pubmed: 11896401doi: 10.1038/nsb770google scholar: lookup
  19. Branger J, van den Blink B, Weijer S, Gupta A, van Deventer SJ, Hack CE, Peppelenbosch MP, van der Poll T. Inhibition of coagulation, fibrinolysis, and endothelial cell activation by a p38 mitogen-activated protein kinase inhibitor during human endotoxemia.. Blood 2003 Jun 1;101(11):4446-8.
    pubmed: 12576315doi: 10.1182/blood-2002-11-3338google scholar: lookup
  20. Branger J, van den Blink B, Weijer S, Madwed J, Bos CL, Gupta A, Yong CL, Polmar SH, Olszyna DP, Hack CE, van Deventer SJ, Peppelenbosch MP, van der Poll T. Anti-inflammatory effects of a p38 mitogen-activated protein kinase inhibitor during human endotoxemia.. J Immunol 2002 Apr 15;168(8):4070-7.
    pubmed: 11937566doi: 10.4049/jimmunol.168.8.4070google scholar: lookup
  21. nNorman P. Metabolic and inflammatory disease R&D: an assessment of 5 highly promising therapeutic classes. Insight Pharma Reports; 2007. nhttp://www.bio-itworld.com/uploadedFiles/Reports/Reports/An_Assessment_of_5_Highly_Promising_Therapeutic_Classes/sample_metabolic.pdf. Accessed April 9, 2020.
  22. Bauquier JR, Tennent-Brown BS, Tudor E, Bailey SR. Anti-inflammatory effects of a p38 MAP kinase inhibitor, doramapimod, against bacterial cell wall toxins in equine whole blood.. Vet Immunol Immunopathol 2020 Feb;220:109994.
    pubmed: 31877483doi: 10.1016/j.vetimm.2019.109994google scholar: lookup
  23. Bauquier JR. Investigating Novel Treatments and Biomarkers for the Systemic Inflammatory Response Syndrome in Horses. Melbourne, Victoria: Faculty of Veterinary and Agricultural Sciences, University of Melbourne; 2018.
  24. Barton MH, Parviainen A, Norton N. Polymyxin B protects horses against induced endotoxaemia in vivo.. Equine Vet J 2004 Jul;36(5):397-401.
    pubmed: 15253079doi: 10.2746/0425164044868350google scholar: lookup
  25. Cudmore LA, Muurlink T, Whittem T, Bailey SR. Effects of oral clenbuterol on the clinical and inflammatory response to endotoxaemia in the horse.. Res Vet Sci 2013 Jun;94(3):682-6.
    pubmed: 23462621doi: 10.1016/j.rvsc.2013.01.003google scholar: lookup
  26. Declue AE, Johnson PJ, Day JL, Amorim JR, Honaker AR. Pathogen associated molecular pattern motifs from Gram-positive and Gram-negative bacteria induce different inflammatory mediator profiles in equine blood.. Vet J 2012 Jun;192(3):455-60.
    pubmed: 21974971doi: 10.1016/j.tvjl.2011.09.001google scholar: lookup
  27. Moore JN, Norton N, Barton MH, Hurley DJ, Reber AJ, Donovan DC, Vandenplas ML, Parker TS, Levine DM. Rapid infusion of a phospholipid emulsion attenuates the effects of endotoxaemia in horses.. Equine Vet J 2007 May;39(3):243-8.
    pubmed: 17520976doi: 10.2746/042516407x173343google scholar: lookup
  28. Morris DD, Crowe N, Moore JN. Correlation of clinical and laboratory data with serum tumor necrosis factor activity in horses with experimentally induced endotoxemia.. Am J Vet Res 1990 Dec;51(12):1935-40.
    pubmed: 2085219
  29. Morris DD, Moore JN, Crowe N, Moldawer LL. Effect of experimentally induced endotoxemia on serum interleukin-6 activity in horses.. Am J Vet Res 1992 May;53(5):753-6.
    pubmed: 1524301
  30. Brooks AC, Menzies-Gow NJ, Wheeler-Jones CP, Bailey SR, Elliott J, Cunningham FM. Regulation of platelet activating factor-induced equine platelet activation by intracellular kinases.. J Vet Pharmacol Ther 2009 Apr;32(2):189-96.
    pubmed: 19290950doi: 10.1111/j.1365-2885.2008.01020.xgoogle scholar: lookup
  31. Badger AM, Bradbeer JN, Votta B, Lee JC, Adams JL, Griswold DE. Pharmacological profile of SB 203580, a selective inhibitor of cytokine suppressive binding protein/p38 kinase, in animal models of arthritis, bone resorption, endotoxin shock and immune function.. J Pharmacol Exp Ther 1996 Dec;279(3):1453-61.
    pubmed: 8968371
  32. Badger AM, Griswold DE, Kapadia R, Blake S, Swift BA, Hoffman SJ, Stroup GB, Webb E, Rieman DJ, Gowen M, Boehm JC, Adams JL, Lee JC. Disease-modifying activity of SB 242235, a selective inhibitor of p38 mitogen-activated protein kinase, in rat adjuvant-induced arthritis.. Arthritis Rheum 2000 Jan;43(1):175-83.
    pubmed: 10643714doi: 10.1002/1529-0131(200001)43:1<175::aid-anr22>3.0.co;2-sgoogle scholar: lookup
  33. Underwood DC, Osborn RR, Kotzer CJ, Adams JL, Lee JC, Webb EF, Carpenter DC, Bochnowicz S, Thomas HC, Hay DW, Griswold DE. SB 239063, a potent p38 MAP kinase inhibitor, reduces inflammatory cytokine production, airways eosinophil infiltration, and persistence.. J Pharmacol Exp Ther 2000 Apr;293(1):281-8.
    pubmed: 10734180
  34. Ono K, Han J. The p38 signal transduction pathway: activation and function.. Cell Signal 2000 Jan;12(1):1-13.
    pubmed: 10676842doi: 10.1016/s0898-6568(99)00071-6google scholar: lookup
  35. Kuma Y, Sabio G, Bain J, Shpiro N, Márquez R, Cuenda A. BIRB796 inhibits all p38 MAPK isoforms in vitro and in vivo.. J Biol Chem 2005 May 20;280(20):19472-9.
    pubmed: 15755732doi: 10.1074/jbc.m414221200google scholar: lookup
  36. Goldstein DM, Kuglstatter A, Lou Y, Soth MJ. Selective p38alpha inhibitors clinically evaluated for the treatment of chronic inflammatory disorders.. J Med Chem 2010 Mar 25;53(6):2345-53.
    pubmed: 19950901doi: 10.1021/jm9012906google scholar: lookup
  37. Clark AR, Dean JL, Saklatvala J. Post-transcriptional regulation of gene expression by mitogen-activated protein kinase p38.. FEBS Lett 2003 Jul 3;546(1):37-44.
    pubmed: 12829234doi: 10.1016/s0014-5793(03)00439-3google scholar: lookup
  38. Brook M, Sully G, Clark AR, Saklatvala J. Regulation of tumour necrosis factor alpha mRNA stability by the mitogen-activated protein kinase p38 signalling cascade.. FEBS Lett 2000 Oct 13;483(1):57-61.
    pubmed: 11033356doi: 10.1016/s0014-5793(00)02084-6google scholar: lookup
  39. Dean JL, Brook M, Clark AR, Saklatvala J. p38 mitogen-activated protein kinase regulates cyclooxygenase-2 mRNA stability and transcription in lipopolysaccharide-treated human monocytes.. J Biol Chem 1999 Jan 1;274(1):264-9.
    pubmed: 9867839doi: 10.1074/jbc.274.1.264google scholar: lookup
  40. Miyazawa K, Mori A, Miyata H, Akahane M, Ajisawa Y, Okudaira H. Regulation of interleukin-1beta-induced interleukin-6 gene expression in human fibroblast-like synoviocytes by p38 mitogen-activated protein kinase.. J Biol Chem 1998 Sep 18;273(38):24832-8.
    pubmed: 9733787doi: 10.1074/jbc.273.38.24832google scholar: lookup
  41. Abraham E. Alterations in cell signaling in sepsis.. Clin Infect Dis 2005 Nov 15;41 Suppl 7:S459-64.
    pubmed: 16237648doi: 10.1086/431997google scholar: lookup
  42. Eckert RE, Neuder LE, Bell JL, Trujillo JC, Jones SL. The role of p38 mitogen-activated kinase (MAPK) in the mechanism regulating cyclooxygenase gene expression in equine leukocytes.. Vet Immunol Immunopathol 2007 Aug 15;118(3-4):294-303.
    pubmed: 17614138doi: 10.1016/j.vetimm.2007.06.001google scholar: lookup
  43. Neuder LE, Keener JM, Eckert RE, Trujillo JC, Jones SL. Role of p38 MAPK in LPS induced pro-inflammatory cytokine and chemokine gene expression in equine leukocytes.. Vet Immunol Immunopathol 2009 Jun 15;129(3-4):192-9.
    pubmed: 19070370doi: 10.1016/j.vetimm.2008.11.006google scholar: lookup
  44. Schreiber S, Feagan B, D'Haens G, Colombel JF, Geboes K, Yurcov M, Isakov V, Golovenko O, Bernstein CN, Ludwig D, Winter T, Meier U, Yong C, Steffgen J. Oral p38 mitogen-activated protein kinase inhibition with BIRB 796 for active Crohn's disease: a randomized, double-blind, placebo-controlled trial.. Clin Gastroenterol Hepatol 2006 Mar;4(3):325-34.
    pubmed: 16527696doi: 10.1016/j.cgh.2005.11.013google scholar: lookup
  45. Yoshigai E, Hara T, Inaba H, Hashimoto I, Tanaka Y, Kaibori M, Kimura T, Okumura T, Kwon AH, Nishizawa M. Interleukin-1β induces tumor necrosis factor-α secretion from rat hepatocytes.. Hepatol Res 2014 May;44(5):571-83.
    pubmed: 23647831doi: 10.1111/hepr.12157google scholar: lookup
  46. Cavaillon JM, Adib-Conquy M, Fitting C, Adrie C, Payen D. Cytokine cascade in sepsis.. Scand J Infect Dis 2003;35(9):535-44.
    pubmed: 14620132doi: 10.1080/00365540310015935google scholar: lookup
  47. van der Poll T, Lowry SF. Tumor necrosis factor in sepsis: mediator of multiple organ failure or essential part of host defense?. Shock 1995 Jan;3(1):1-12.
    pubmed: 7850574doi: 10.1097/00024382-199501000-00001google scholar: lookup
  48. Dinarello CA. Interleukin-1, interleukin-1 receptors and interleukin-1 receptor antagonist.. Int Rev Immunol 1998;16(5-6):457-99.
    pubmed: 9646173doi: 10.3109/08830189809043005google scholar: lookup
  49. Iwano S, Asaoka Y, Akiyama H, Takizawa S, Nobumasa H, Hashimoto H, Miyamoto Y. A possible mechanism for hepatotoxicity induced by BIRB-796, an orally active p38 mitogen-activated protein kinase inhibitor.. J Appl Toxicol 2011 Oct;31(7):671-7.
    pubmed: 21328587doi: 10.1002/jat.1622google scholar: lookup
  50. Pittet D, Thiévent B, Wenzel RP, Li N, Gurman G, Suter PM. Importance of pre-existing co-morbidities for prognosis of septicemia in critically ill patients.. Intensive Care Med 1993;19(5):265-72.
    pubmed: 8408935doi: 10.1007/bf01690546google scholar: lookup
  51. Cohen SB, Cheng TT, Chindalore V, Damjanov N, Burgos-Vargas R, Delora P, Zimany K, Travers H, Caulfield JP. Evaluation of the efficacy and safety of pamapimod, a p38 MAP kinase inhibitor, in a double-blind, methotrexate-controlled study of patients with active rheumatoid arthritis.. Arthritis Rheum 2009 Feb;60(2):335-44.
    pubmed: 19180516doi: 10.1002/art.24266google scholar: lookup
  52. Genovese MC. Inhibition of p38: has the fat lady sung?. Arthritis Rheum 2009 Feb;60(2):317-20.
    pubmed: 19180514doi: 10.1002/art.24264google scholar: lookup
  53. Hammaker D, Firestein GS. "Go upstream, young man": lessons learned from the p38 saga.. Ann Rheum Dis 2010 Jan;69 Suppl 1(Suppl 1):i77-82.
    pmc: PMC2911016pubmed: 19995751doi: 10.1136/ard.2009.119479google scholar: lookup
  54. Jacobs CC, Holcombe SJ, Cook VL, Gandy JC, Hauptman JG, Sordillo LM. Ethyl pyruvate diminishes the inflammatory response to lipopolysaccharide infusion in horses.. Equine Vet J 2013 May;45(3):333-9.
    pubmed: 22943507doi: 10.1111/j.2042-3306.2012.00634.xgoogle scholar: lookup
  55. Peiró JR, Barnabé PA, Cadioli FA, Cunha FQ, Lima VM, Mendonça VH, Santana AE, Malheiros EB, Perri SH, Valadão CA. Effects of lidocaine infusion during experimental endotoxemia in horses.. J Vet Intern Med 2010 Jul-Aug;24(4):940-8.
    pubmed: 20649751doi: 10.1111/j.1939-1676.2010.0555.xgoogle scholar: lookup
  56. Poulin Braim AE, MacDonald MH, Bruss ML, Grattendick KJ, Giri SN, Margolin SB. Effects of intravenous administration of pirfenidone on horses with experimentally induced endotoxemia.. Am J Vet Res 2009 Aug;70(8):1031-42.
    pubmed: 19645586doi: 10.2460/ajvr.70.8.1031google scholar: lookup
  57. Song GY, Chung CS, Jarrar D, Chaudry IH, Ayala A. Evolution of an immune suppressive macrophage phenotype as a product of P38 MAPK activation in polymicrobial sepsis.. Shock 2001 Jan;15(1):42-8.
    pubmed: 11198356doi: 10.1097/00024382-200115010-00007google scholar: lookup

Citations

This article has been cited 7 times.
  1. Fu X, Sun X, Zhang C, Lv N, Guo H, Xing C, Lv J, Wu J, Zhu X, Liu M, Su L. Genkwanin Prevents Lipopolysaccharide-Induced Inflammatory Bone Destruction and Ovariectomy-Induced Bone Loss. Front Nutr 2022;9:921037.
    doi: 10.3389/fnut.2022.921037pubmed: 35811983google scholar: lookup
  2. Liu J, Li T, Xin L, Li X, Zhang J, Zhu P. Comprehensive characterization of multi-omics landscapes between gut microbial metabolites and the druggable genome in sepsis. Front Immunol 2025;16:1597676.
    doi: 10.3389/fimmu.2025.1597676pubmed: 40761792google scholar: lookup
  3. Yan H, Cheng C, Song Y, Luo L, Liu D, Zhang D. Revealing the Process of Vein Graft Failure: A Panoramic Review from Etiology Analysis to Mechanism Explanation and Treatment Strategy. Cardiovasc Drugs Ther 2025 May 29;.
    doi: 10.1007/s10557-025-07711-3pubmed: 40439962google scholar: lookup
  4. Liu Z, Ting Y, Li M, Li Y, Tan Y, Long Y. From immune dysregulation to organ dysfunction: understanding the enigma of Sepsis. Front Microbiol 2024;15:1415274.
    doi: 10.3389/fmicb.2024.1415274pubmed: 39252831google scholar: lookup
  5. Li Y, Wu Z, Ding T, Zhang W, Guo H, Huang F. Comprehensive bioinformatics analysis and cell line experiments revealed the important role of CDCA3 in sarcoma. Heliyon 2024 Jul 15;10(13):e32785.
    doi: 10.1016/j.heliyon.2024.e32785pubmed: 39035484google scholar: lookup
  6. Wang Z, Zhang Y, Yang X, Zhang T, Li Z, Zhong Y, Fang Y, Chong W, Chen H, Lu M. Genetic and molecular characterization of metabolic pathway-based clusters in esophageal squamous cell carcinoma. Sci Rep 2024 Mar 14;14(1):6200.
    doi: 10.1038/s41598-024-56391-wpubmed: 38486026google scholar: lookup
  7. Gao Y, Packeiser EM, Wendt S, Sekora A, Cavalleri JV, Pratscher B, Alammar M, Hühns M, Brenig B, Junghanss C, Nolte I, Murua Escobar H. Cross-Species Comparison of the Pan-RAF Inhibitor LY3009120's Anti-Tumor Effects in Equine, Canine, and Human Malignant Melanoma Cell Lines. Genes (Basel) 2024 Feb 3;15(2).
    doi: 10.3390/genes15020202pubmed: 38397192google scholar: lookup
Subscribe to our newsletter
Join 99,357 horse owners like you who receive our email updates on horse health and nutrition.