Skip to main content

Advertisement

SpringerLink
Log in

A new insight into effects of a clinically proved combination of methotrexate and hydroxychloroquine

  • Original Paper
  • Published:
Monatshefte für Chemie - Chemical Monthly Aims and scope Submit manuscript

Abstract

Combination of methotrexate (MTX) with hydroxychloroquine (HCQ) is one of the most effective therapies used for treatment of rheumatoid arthritis. The aim of the study was to more complexly examine the effect of combination HCQ and MTX on disease progression in arthritic rats focusing on inflammatory markers. Adjuvant arthritis (AA) was induced by intradermal injection of Mycobacterium butyricum in incomplete Freund´s adjuvant in Lewis rats and the disease was monitored 28 days. The experiment included healthy animals, control AA animals, AA animals with administration of HCQ (40 mg/kg b.w. daily, p.o.), AA animals with administration of MTX (0.4 mg/kg b.w. twice a week, p.o.), and AA animals treated with the combination of HCQ + MTX. HCQ in monotherapy reduced only the plasmatic level of IL-1β (day 28). On day 14, MTX + HCQ significantly decreased the plasmatic levels of IL-1β, IL-17 and combination was more effective than MTX in reduction of IL-17. On day 28, combination significantly decreased the plasmatic levels of CRP and IL-1β and it was more effective than MTX in reduction of IL-1β. Expression of IL-1β and inducible NO-synthase total mRNA in lung were most effectively reduced by MTX + HCQ. Combination of MTX + HCQ reduced hind paw volume, arthritic score and increased body mass of animals very effectively (days 14, 21, and 28). In summary, MTX + HCQ were much better than MTX in correcting inflammatory and clinical markers. This study showed in more details that the anti-arthritic effect of MTX + HCQ is particularly due to reduction of the levels of inflammatory cytokines.

Graphical Abstract

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

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Fig. 1
Fig. 2
Fig. 3
Fig. 4

Similar content being viewed by others

References

  1. Ben-Zvi I, Kivity S, Langevitz P, Shoenfeld Y (2012) Clin Rev Allergy Immunol 42:145

    Article  CAS  Google Scholar 

  2. Kalia S, Dutz JP (2007) Dermatol Ther 20:160

    Article  Google Scholar 

  3. Ohkuma S, Poole B (1978) Proc Natl Acad Sci USA 75:3327

    Article  CAS  Google Scholar 

  4. Ziegler HK, Unanue ER (1982) Proc Natl Acad Sci USA 79:175

    Article  CAS  Google Scholar 

  5. Sperber K, Quraishi H, Kalb TH, Panja A, Stecher V, Mayer L (1993) J Rheumatol 20:803

    CAS  Google Scholar 

  6. Loffler BM, Bohn E, Hesse B, Kunze H (1985) Biochim Biophys Acta 835:448

    Article  CAS  Google Scholar 

  7. Manku MS, Horrobin DF (1976) Lancet 2:1115

    Article  CAS  Google Scholar 

  8. Cohen SN, Yielding KL (1965) J Biol Chem 240:3123

    CAS  Google Scholar 

  9. Goldman FD, Gilman AL, Hollenback C, Kato RM, Premack BA, Rawlings DJ (2000) Blood 95:3460

    CAS  Google Scholar 

  10. Lesiak A, Narbutt J, Sysa-Jedrzejowska A, Lukamowicz J, McCauliffe DP, Wozniacka A (2010) Lupus 19:683

    Article  CAS  Google Scholar 

  11. Kyburz D, Brentano F, Gay S (2006) Nat Clin Pract Rheumatol 2:458

    Article  Google Scholar 

  12. Tian H, Cronstein BN (2007) Bull NYU Hosp Jt Dis 65:168

    Google Scholar 

  13. Montesinos MC, Desai A, Delano D, Chen JF, Fink JS, Jacobson MA, Cronstein BN (2003) Arthritis Rheumatol 48:240

    Article  CAS  Google Scholar 

  14. Baggott JE, Morgan SL, Vaughn WH (1994) Biochem J 300:627

    Article  CAS  Google Scholar 

  15. Montesinos MC, Takedachi M, Thompson LF, Wilder TF, Fernández P, Cronstein BN (2007) Arthritis Rheumatol 56:1440

    Article  CAS  Google Scholar 

  16. Montesinos MC, Yap JS, Desai A, Posadas I, McCrary CT, Cronstein BN (2000) Arthritis Rheumatol 43:656

    Article  CAS  Google Scholar 

  17. Genestier L, Paillot R, Fournel S, Ferraro C, Miossec P, Revillard JP (1998) J Clin Invest 102:322

    Article  CAS  Google Scholar 

  18. Bernini JC, Fort DW, Griener JC, Kane BJ, Chappell WB, Kamen BA (1995) Lancet 345:544

    Article  CAS  Google Scholar 

  19. Mirabet M, Herrera C, Cordero OJ, Mallol J, Lluis C, Franco R (1999) J Cell Sci 112:491

    CAS  Google Scholar 

  20. Kuncirova V, Ponist S, Mihalova D, Drafi F, Nosal R, Acquaviva A, Gardi C, Harmatha J, Hradkova I, Bauerova K (2014) Fundam Clin Pharmacol 28:616

    Article  CAS  Google Scholar 

  21. Dale J, Alcorn N, Capell H, Madhok R (2007) Nat Clin Pract Rheumatol 3:450

    Article  CAS  Google Scholar 

  22. Connolly KM, Stecher VJ, Danis E, Pruden DJ, LaBrie T (1988) Int J Immunopharmacol 10:717

    Article  CAS  Google Scholar 

  23. Trnavský K, Gatterová J, Lindusková M, Pelisková Z (1993) Z Rheumatol 52:292

    Google Scholar 

  24. Ridker PM (2001) Eur Heart J 22:2135

    Article  CAS  Google Scholar 

  25. Kudo O, Fujikawa Y, Itonaga I, Sabokbar A, Torisu T, Athanasou NA (2002) J Pathol 198:220

    Article  CAS  Google Scholar 

  26. Dayer JM (2003) Rheumatology (Oxford) 42:3

    Article  Google Scholar 

  27. DiMartino MJ, Johnson WJ, Votta B, Hanna N (1987) Agents Actions 21:348

    Article  CAS  Google Scholar 

  28. Seitz M, Loetscher P, Dewald B, Towbin H, Rordorf C, Gallati H, Baggiolini M, Gerber NJ (1995) Br J Rheumatol 34:602

    Article  CAS  Google Scholar 

  29. Tabarkiewicz J, Pogoda K, Karczmarczyk A, Pozarowski P, Giannopoulos K (2015) Arch Immunol Ther Exp 63:435

    Article  CAS  Google Scholar 

  30. Stolina M, Bolon B, Middleton S, Dwyer D, Brown H, Duryea D, Zhu L, Rohner A, Pretorius J, Kostenuik P, Feige U, Zack D (2009) J Clin Immunol 29:158

    Article  CAS  Google Scholar 

  31. Hayashida K, Nanki T, Girschick H, Yavuz S, Ochi T, Lipsky PE (2001) Arthritis Res 3:118

    Article  CAS  Google Scholar 

  32. Lopez-Castejon G, Brough D (2011) Cytokine Growth Factor Rev 22:189

    Article  CAS  Google Scholar 

  33. Hymowitz SG, Filvaroff EH, Yin JP, Lee J, Cai L, Risser P, Maruoka M, Mao W, Foster J, Kelley RF, Pan G, Gurney AL, de Vos AM, Starovasnik MA (2001) EMBO J 20:5332

    Article  CAS  Google Scholar 

  34. Thompson D, Pepys MB, Wood SP (1999) Structure 7:169

    Article  CAS  Google Scholar 

  35. Yunt ZX, Solomon JJ (2015) Rheum Dis Clin North Am 41:225

    Article  Google Scholar 

Download references

Acknowledgements

This work was supported by grants APVV-0052-10, APPV-15-308, and VEGA 2/0045/11.

Author information

Authors and Affiliations

  1. Institute of Experimental Pharmacology and Toxicology, Centre of Experimental Medicine of the Slovak Academy of Sciences, Dubravska cesta 9, 841 04, Bratislava, Slovak Republic

    Silvester Poništ, Viera Kuncírová, Lukáš Slovák, Danica Mihalová, Viera Jančinová, Radomír Nosáľ & Katarína Bauerová

  2. Department of Cell and Molecular Biology of Drugs, Faculty of Pharmacy, Comenius University, Odbojarov 10, 832 32, Bratislava, Slovak Republic

    Ľudmila Pašková & Katarína Bauerová

Authors
  1. Silvester Poništ
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Viera Kuncírová
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Ľudmila Pašková
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Lukáš Slovák
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Danica Mihalová
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Viera Jančinová
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Radomír Nosáľ
    View author publications

    You can also search for this author in PubMed Google Scholar

  8. Katarína Bauerová
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding authors

Correspondence to Silvester Poništ or Katarína Bauerová.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Poništ, S., Kuncírová, V., Pašková, Ľ. et al. A new insight into effects of a clinically proved combination of methotrexate and hydroxychloroquine. Monatsh Chem 149, 961–967 (2018). https://doi.org/10.1007/s00706-018-2178-y

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00706-018-2178-y

Keywords

Search

Navigation