Abstract
The efficacy of combination therapy with methotrexate (MTX) and probiotic bacteriaEnterococcus faecium enriched with organic selenium (EFSe) in rats with adjuvant arthritis was determined. Rats with adjuvant arthritis were given MTX (0.3 mg/kg 2-times weekly, orally); lyophilizedE. faecium enriched with Se (15 mg/kg, 5 d per week, orally); and a combination of MTX plus EFSe for a period of 50 d from the immunization. Levels of serum albumin, serum nitrite/nitrate concentrations, changes in hind paw swellling, arthrogram score, bone erosions, whole body bone mineral density (BMD) and bone mineral content (BMC) were assayed in the rats as variables of inflammation and destructive arthritis-associated changes. Treatment with MTX and with the combination MTX+EFSe significantly inhibited markers of both inflammation and arthritis. Significant differences in favor of combination therapy with MTX+EFSe as compared to MTX alone were seen in serum albumin concentration, hind paw swelling and arthrogram score. Reductions in radiographic scores were also more pronounced in the combination therapy group. Combination therapy, but not MTX alone, inhibited the reduction of BMD and BMC; treatment with lyophilized EFSe alone had no significant effect on adjuvant arthritis in rats. The potent therapeutic effect of low dosage MTX therapy in combination with lyophilized EFSe on adjuvant arthritis in rats was shown.
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Baggott J.E., Morgan S.L., Koopman W.J.: The effect of methotrexate and 7-hydroxymethotrexate on rat adjuvant arthritis and on urinary aminoimidazole carboxamide excretion.Arthritis Rheum..41, 1407–1410 (1998).
Belicová, A., Krajĉoviĉ J., Dobias J., Ebringer L.: Antimutagenicity of milk fermented byEnterococcus faecium Folia Microbiol.,44, 513–518 (1999).
Bloemendal A., Van der Zee R., Rutten V.P., van Kooten P.J., Farine J.C., van Eden W.: Experimental immunization with antirheumatic bacterial extract OM-89 induces T cell responses to heat shock protein (hsp) 60 and hsp 70; modulation of peripheral immunological tolerance as its possible mode of action in the treatment of rheumatoid arthritis (RA).Clin. Exp. Immunol..110, 72–78 (1997).
Bonnet J., Zerath E., Picaud N., Lesur C., Mattio A., Tordjman C., Hott M., Marie P.J.: Bone morphometric changes in adjuvant-induced polyarthritic osteopenia in rats: evidence for an early bone formation defect.,J. Bone Miner. Res.,8, 659–668 (1993).
Cannon G.W., Openshaw S.J., Hibbs J.B., Jr.,Hoidal J.R., Huecksteadt T.P., Griffiths M.M.: Nitric oxide production during adjuvant-induced and collagen induced arthritis.,Arthritis Rheum.,39, 1677–1684 (1996).
Connolly K.M., Stecher V.J., Danis E., Pruden D.J., LaBrie T.: Alteration of interleukin-1 production and the acute phase response following medication of adjuvant arthritic rats with cyclosporin A or methotrexate.Internal J. Immunopharmacol.,10, 717–728 (1988a).
Connolly K.M., Stecher V.J., LaBrie T., Fluno C.: Modulation of the acute phase response andin vitro measurement of interleukin-1 activity following administration of dexamethasone to adjuvant-arthritic rats.Immunopharmacology15, 133–142 (1988b).
Constantin A., Loubet-Lescoulié P., Lambert N., Yassine-Diab B., Abbal M., Maziéres B., de Préval C., Cantagrel A.: Antiinflammatory and immunoregulatory action of methotrexate in the treatment of rheumatoid arthritis. Evidence of increased interleukin-4 and interleukin-10 gene expression demonstratedin vitro competitive reverse transcriptase-polymerase chain reaction.Arthritis Rheum.,41, 48–57 (1998).
Cortas N.K., Waking N.W.: Determination of inorganic nitrate in serum and urine by a kinetic cadmium-reduction method.Clin. Chem.36, 1440–1443 (1990).
Cronstein B.N., Naime D., Ostad E.: The anti-inflammatory mechanism of methotrexate: increased adenosine release at inflamed sites diminishes leukocyte accumulation anin vivo model of inflammations.J. Clin. Invest.,92, 2675–2682 (1993).
Ferenčík M., Mikeŝ Z., Ebringer L., Jahnová E., Ĉižnár I.: Immunostimulatory and other beneficial health effects of lactic acid bacteria.Bratisl. Lek. Listry101, 51–53 (2000).
Grabowski P.S., England A.J., Dykhuizen R., Copland M., Benjamin N., Reid D. M., Ralston S.H.: Elevated nitric oxide production in rheumatoid arthritis: detection using the fasting urinary nitrate: creatinine ratio.Arthritis Rheum.,39, 643–647 (1996).
Hirata S., Matsubara T., Saura R., Tateishi H., Hirohota K.: Inhibition ofin vitro vascular endothelial cell proliferation andin vivo neovascularisation by low-dose methotrexate.Arthritis Rheum.,32, 1065–1073 (1989).
Jaffee B.D., Kerr J.S., Jones E.A., Giannaras J.V., McGowan M., McGowan M., Ackerman N.R.: The effect of immunomodulating drugs on adjuvant-induced arthritis in Lewis rats.Agent Actions,27, 344–346 (1989).
Kawai S., Nagai K., Nishida S., Sakio K., Murai E., Mizushima Y.: Low-dose pulse methotrexate inhibits articular destruction of adjuvant arthritis in rats.J. Pharm. Pharmacol.,49, 213–215 (1997).
Lauková A., Mareková M.: Production of bacteriocins by different enterococcal isolates.Folia Microbiol.46, 49–52 (2001).
Lauková A., Vlaemynck G., Czikková S.: Effect of enterocin CCM 4231 onListeria monocytogenes in Saint-Paulin cheese.Folia Microbiol.,46, 157–160 (2001).
Mikeš Z., Ferenčík M., Jahnová E., Ebringer L., Ĉižnár I.: Hypocholesteloremic and immunostimulatory effects of orally appliedEnterococcus faecium M-74 in man.Folia Microbiol.,40, 639–646 (1995).
Morgan S.L., Baggott J.E., Bernreuter W.K., Gay R.E., Arani R., Alarcón G.S.: MTX affects inflammation and tissue destruction differently in the rat AA model.J. Rheumatol.,28, 1476–1481 (2001).
Nakajima A., Hakoda M., Yamanaka H., Kamatani N., Kashiwazaki S.: Divergent effects of methotrexate on the clonal growth of T and B lymphocytes and synovial adherent cells from patients with rheumatoid arthritis.Ann. Rheum. Dis.,55, 237–242 (1996).
O'Dell J.R.: Methotrexate use in rheumatoid arthritis.Rheum. Dis. Clin. N. Am.,23, 779–796 (1997).
Omata T., Segawa Y., Inoue N., Tsuzuike N., Itokazu Y., Tamaki H: Methotrexate suppresses nitric oxide productionex vivo in macrophages from rats with adjuvant-induced arthritis.Res. Exp. Med.,197, 81–90 (1997).
Oyanagui Y.: Nitric oxide and superoxide radical are involved in both initiation and development of adjuvant arthritis in rats.Life Sci,54, PL285-PL289 (1994).
Parnham M., Winkelmann J., Leyck S.: Macrophage, lymphocyte and chronic inflammatory response in selenium deficient rodents. Association with decreased glutatione peroxidase activity.Internat. J. Immunopharmacol.,5, 455–461 (1983).
Pearson C.M., Wood F.: Studies of arthritis and other lesions induced in rats by the injection of mycobacterial adjuvant—VII. Pathogenic details of the arthritis and spondylitis.Amer. J. Pathol.,42, 73–95 (1963).
Peretz A., Siderova V., Neve J.: Selenium supplementation in rheumatoid arthritis investigated in a double blind, placebo-controlled trials.Scand. J. Rheumatol.,30, 208–212 (2001).
Ridge S., Ferguson K.S., Rath N., Galivan J., Freisheim J.H., Oronsky A.L., Kerwar S.S.: Methotrexate suppresses passive adjuvant arthritis: studies on the metabolism of methotrexate in mononuclear cells derived from normal and adjuvant arthritic rats.J. Rheumatol.,15, 1193–1197 (1988).
Segal M., Mozes E., Yaron M., Tartakovski B.: The effect of methotrexate on the production and activity of interleukin—I.Arthritis Rheum.32, 370–377 (1989).
Stamler J.S., Singel D.J., Loscalzo J.: Biochemistry of nitric oxide and its redox-activated forms.Science,258, 1898–1902 (1992).
Stefanovic-Racic M., Meyers K., Meschter C., Coffey J.W., Hoffman R.A., Evans C.H.: Comparison of the nitric oxide synthase inhibitors methylarginine and aminoguanidine as prophylactic and therapeutic agents in rat adjuvant arthritis.J. Rheumatol.,22, 1992–1998 (1995).
Suarez C.R., Pickett W.C., Bell D.H., McClintock D.K., Oronsky A.L., Kerwar S.S.: Effect of low dose methotrexate on neutrophil chemotaxis induced by leukotriene B4 and component C5a.J. Rheumatol.,14, 9–11 (1987).
Suzuki Y., Nakagawa M., Masuda C., Ide M., Uehara R., Ichikawa Y., Mizushima Y.: Short term low dose methotrexate ameliorates abnormal bone metabolism and bone loss in adjuvant induced arthritis.J. Rheumatol.,24, 1890–1895 (1997).
Taurog J.D., Sandberg G.P., Mahowald M.L.: The cellular basis of adjuvant arthritis—II. Characterization of the cells mediating passive transfer.Cell Immunol.,80, 198–204 (1983).
Trebichavský I., Zídek Z., Franková D., Zahradníĉková M., Ŝplíchal I.: Nitric oxide metabolites in gnotobiotic piglets orally infected withSalmonella enterica serovar typhimurium.Folia Microbiol.46, 353–358 (2001).
Ueki Y., Miyake S., Tominaga Y, Eguchi K.: Increased nitric oxide levels in patients with rheumatoid arthritis.J. Rheumatol.,23, 230–236 (1996).
Welles W.L., Silkworth J., Oronsky A.L., Kerwar S.S., Galivan J.: Studies on the effect of low dose methotrexate in adjuvant arthritis.J. Rheumatol.,12, 904–906 (1985).
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Rovenský, J., Švík, K., Stančíková, M. et al. Treatment of experimental adjuvant arthritis with the combination of methotrexate and lyophilizedEnterococcus faecium enriched with organic selenium. Folia Microbiol 47, 573–578 (2002). https://doi.org/10.1007/BF02818800
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DOI: https://doi.org/10.1007/BF02818800