JIBTVA  Vol.4 No.1 , January 2015
Comparative Clinical Trial of Antibodies to Interferon-Gamma (IFN-γ) and Tumor Necrosis Factor-Alpha (TNF-α) in the Treatment of Rheumatoid Arthritis
ABSTRACT
In 1974, in Nature, one of us has proposed a radically new idea that led to the development of anticytokine therapy which is now used around the world for the treatment of autoimmune diseases. We were the first to use antibodies to IFN-γ and were some of the first to suggest using antagonists of TNF-α in the treatment of autoimmune and inflammatory diseases as well. Our method suppresses one of the main pathogenetic mechanisms of these diseases. Antibodies to IFN-γ and TNF-α exhibit dramatic effects on clinical manifestations of rheumatoid arthritis (RA). However, in our trial ultrasound assessment of the synovial membrane thickness in RA patients showed that only anti-IFN-γ exerted pronounced anti-inflammatory effect. Some patients who underwent treatment with antibodies to TNF-α developed a number of complications. Anticytokine therapy (mono- and poly-) alone or in combination with other drugs can possibly be used not only in the treatment of autoimmune diseases, but also in other pathologies with cytokine synthesis disturbances (a number of neurological, psychiatric, endocrine, and other diseases).

Cite this paper
Skurkovich, S. , Lukina, G. , Sigidin, Y. , Pushkova, O. , Mach, E. and Skurkovich, B. (2015) Comparative Clinical Trial of Antibodies to Interferon-Gamma (IFN-γ) and Tumor Necrosis Factor-Alpha (TNF-α) in the Treatment of Rheumatoid Arthritis. Journal of Immune Based Therapies, Vaccines and Antimicrobials, 4, 1-8. doi: 10.4236/jibtva.2015.41001.
References
[1]   Skurkovich, S.V., Klimova, K.G., Eremkina, E.I., et al. (1974) Immunosuppressive Effect of an Anti-Interferon Serum. Nature, 247, 551-552.
http://dx.doi.org/10.1038/247551a0

[2]   Skurkovich, S.V. and Eremkina, E.I. (1975) Probable role of Interferon in Allergy. Annals of Allergy, 35, 356-360.

[3]   Skurkovich, S.V., Loukina, G.V., Sigidin, Y.A. and Skurkovich, B. (1998) Successful First-Time Use of Antibodies to Interferon-Gamma Alone and Combined with Antibodies to Tumor Necrosis Factor-Alfa to Treat Rheumatic Diseases (Rheumatoid Arthritis, Systemic Lupus Erythematosus, Psoriatic Arthritis, Behcet’s Syndrome). International Journal of Immunotherapy, 14, 23-32.

[4]   Sigidin, Y.A., Loukina, G.V., Skurkovich, B. and Skurkovich, S. (2001) Randomized, Double-Blind Trial of Anti-Interferon-γ Antibodies in Rheumatoid Arthritis. Scandinavian Journal of Rheumatology, 30, 203-207.
http://dx.doi.org/10.1080/030097401316909530

[5]   Skurkovich, S.V. and Skurkovich, B. (1989) Development of Autoimmune Diseases Is Connected with the Initial Disturbance of IFN Synthesis in the Cells. Journal of Intrerferon Research, 9, S305.

[6]   Elliott, M.J., Maini, R.N. and Feldmann, M. (1994) Randomized Double-Blind Comparison of Chimeric Monoclonal Antibody to Tumor Necrosis Factor Alpha (cA2) versus Placebo in Rheumatoid Arthritis. Lancet, 344, 1105-1110.
http://dx.doi.org/10.1016/S0140-6736(94)90628-9

[7]   Skurkovich, S., Skurkovich, B. and Bellanti, J.A. (1987) A Unifying Model of the Immunoregulatory Role of the Interferon System: Can Interferon Produce Disease in Humans? Clinical Immunology and Immunopathology, 43, 362- 373.
http://dx.doi.org/10.1016/0090-1229(87)90146-2

[8]   Vandana, T. and Bhupinder, S.K. (2007) Cytokines and Anti-Cytokines as Therapeutics—An Update. European Journal of Pharmacology, 579, 1-12.

[9]   Billiau, A. (1996) Interferon-γ in Autoimmunity. Cytokine & Growth Factor Reviews, 7, 25-34.
http://dx.doi.org/10.1016/1359-6101(96)00004-4

[10]   Dayer, J.M. (1992) Cytokines, Soluble Cytokine Receptors and Cytokine Receptor Antagonists. EULAR Bulletin, 21, 7-14.

[11]   Dolhain, R.J.E.M., Ter Haar, N.T., Hoefakker, S., Tak, P.P., De Ley, M., Claassen, E., et al. (1996) Increased Expression of Interferon (IFN)-Gamma Together with IFN-Gamma Receptor in the Rheumatoid Synovial Membrane Compared with Synovium of Patients with Osteoarthritis. British Journal of Rheumatology, 35, 24-32.
http://dx.doi.org/10.1093/rheumatology/35.1.24

[12]   Duff, G.W. (1994) Cytokines and Acute Phase Proteins in Rheumatoid Arthritis. Scandinavian Journal of Rheumatology, 23, 9-19.
http://dx.doi.org/10.3109/03009749409095197

[13]   Skurkovich, S., Skurkovich, B. and Kelly, J. (2002) Anticytokine Therapy—New Approach to the Treatment of Autoimmune and Cytokine-Disturbance Diseases. Medical Hypotheses, 59, 770-780.
http://dx.doi.org/10.1016/S0306-9877(02)00346-8

[14]   German Lymphokine Study Group (1992) Double Blind Controlled Phase III Multicenter Clinical Trial with Interferon Gamma in Rheumatoid Arthritis. Rheumatology International, 12, 175-185.
http://dx.doi.org/10.1007/BF00302149

[15]   Cannon, G.W., Emkey, R.D., Denes, A., Cohen, S.A., Saway, P.A., Wolfe, F., et al. (1993) Prospective 5-Year Follow-Up of Recombinant Interferon-Gamma in Rheumatoid Arthritis. The Journal of Rheumatology, 20, 1867-1873.

[16]   Veys, E. (1997) Interferon-Gamma in the Treatment of Rheumatoid Arthritis. In: Strand, V., et al., Eds., Novel Therapeutic Agents in the Treatment of Autoimmune Diseases, Marcel Dekker, Inc., New York.

[17]   Canete, J.D., Martínez, S.E., Farrés, J., Sanmartí, R., Blay, M., Gómez, A., et al. (2000) Differential Th1/Th2 Cytokine Patterns in Chronic Arthritis: Interferon Gamma Is Highly Expressed in Synovium of Rheumatoid Arthritis Compared with Seronegative Spondyloarthropathies. Annals of the Rheumatic Diseases, 59, 263-268.
http://dx.doi.org/10.1136/ard.59.4.263

[18]   Koga, T., Duan, H., Urabe, K. and Furue, M. (2002) In Situ Localization of IFN-Gamma-Positive Cells in Psoriatic Lesional Epidermis. European Journal of Dermatology, 12, 20-23.

[19]   Sato-Kawamura, M., Aiba, S. and Tagami, H. (2003) Strong Expression of CD40, CD54 and HLA-DR Antigen and Lack of Evidence for Direct Cellular Cytotoxicity Are Unique Immunohistopathological Features in Alopecia Areata. Archives of Dermatological Research, 294, 536-543.

[20]   Skurkovich, S., Boiko, A., Beliaeva, I., Buglak, A., Alekseeva, T., Smirnova, N., et al. (2001) Randomized Study of Antibodies to IFN-γ and TNF-α in Secondary Progressive Multiple Sclerosis. Multiple Sclerosis, 7, 277-284.

[21]   Skurkovich, S.V., Volkov, I.E., Delyagin, V.M., Rumyantzev, A.G. and Skurkovich, B. (2003) First Use of Anti-Interferon (IFN)-g in the Treatment of Type I Diabetes in Children. Proceedings of the 8th International Workshop on Autoantibodies and Autoimmunity Conference, Berlin, 10-13 September 2003.

[22]   Skurkovich, S., Korotky, N., Sharova, N. and Skurkovich, B. (2002) Anti-Interferon-g to Treat Alopecia Areata, Psoriasis Vulgaris, Vitiligo, Pemphigus Vulgaris, and Epidermolysis Bullosa. Proceedings of the 5th Asia Pacific Congress of Allergology and Clinical Immunology (APCASI), Seoul, 12-15 October 2002, 121-125.

[23]   Skurkovich, S., Kasparov, A., Narbut, N. and Skurkovich, B. (2002) Treatment of Corneal Transplant Rejection in Humans with Anti-Interferon-γ Antibodies. American Journal of Ophthalmology, 133, 136-137.
http://dx.doi.org/10.1016/S0002-9394(02)01433-2

[24]   Serono Announces Discontinuation of Onercept in Moderate-to Severe Psoriasis and Canvaxin TM in Stage IV Melanoma.
http://www.prnewswire.com/news-releases/serono-announces-discontinuation-of-onercept-in-moderate-to-severe-psoriasis-and-canvaxintm-in-stage-iv-melanoma-66652342.html

[25]   Scheinfeld, N. (2004) A Comprehensive Review and Evaluation of the Side Effects of the Tumor Necrosis Factor Alpha Blockers Etanercept, Infliximab and Adalimumab. Journal of Dermatological Treatment, 15, 280-294.
http://dx.doi.org/10.1080/09546630410017275

 
 
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