caa a22 4500 475845870 CHVBK 20180406123914.0 cr unu---uuuuu 170329e20000901xx s 000 0 eng 10.1007/PL00000629 doi (NATIONALLICENCE)springer-10.1007/PL00000629 Anti-interleukin-1 and anti-tumor necrosis factor-α synergistically inhibit adjuvant arthritis in Lewis rats [Elektronische Daten] [U. Feige*, Y.-L. Hu, J. Gasser, G. Campagnuolo, L. Munyakazi, B. Bolon] Abstract.: Interleukin-1 (IL-1) and tumor necrosis factor-α (TNF-α) play dominant roles in mediating the progression of many inflammatory joint diseases, including rheumatoid arthritis in humans, collagen-induced arthritis in mice and rats, and adjuvant arthritis in rats. Blockade of either cytokine partially controls these diseases. The present study investigated the value of combination anti-cytokine therapy in arthritis: the efficacy of IL-1 receptor antagonist (IL-1ra) and 30 kDa polyethylene glycol (PEG)-conjugated soluble TNF receptor type I (PEG sTNF-RI) given together was assessed in Lewis rats with adjuvant arthritis. Administration of either IL-1ra or PEG sTNF-RI partially alleviated joint inflammation, loss of bone mineral density, and loss of body weight. In contrast, combination of these anti-cytokine treatments exhibited a synergistic capacity to inhibit these changes, even when combining doses of IL-1ra and PEG sTNF-RI that did not affect lesion severity when used alone. Statistical analysis of these adjuvant arthritis data using the isobologram method proved that IL-1ra and PEG sTNF-RI were clearly synergistic in inhibiting inflammation, loss of bone mineral density, loss of body weight, and histopathologic parameters of inflammation and joint destruction. These results suggest that treating autoimmune arthritic diseases with combinations of anti-IL-1 and anti-TNF molecules will achieve superior efficacy compared to the use of a single class of anti-cytokine agent and may allow for dose reductions that could prove useful in minimizing potential side effects. Birkhäuser Verlag Basel,, 2000 Key words. Rheumatoid arthritis nationallicence interleukin 1 nationallicence tumor necrosis factor nationallicence cytokine nationallicence rat nationallicence adjuvant arthritis nationallicence IL-1ra nationallicence soluble receptor nationallicence Feige* U. Department of Pharmacology/Pathology, Amgen, One Amgen Center Drive, M/S 15-2-A, Thousand Oaks (California 91320-1789, USA), Fax +1 805 499 75 06, e-mail: ufeige@amgen.com, US aut Hu Y.-L Department of Pharmacology/Pathology, Amgen, One Amgen Center Drive, M/S 15-2-A, Thousand Oaks (California 91320-1789, USA), Fax +1 805 499 75 06, e-mail: ufeige@amgen.com, US aut Gasser J. Department of Pharmacology/Pathology, Amgen, One Amgen Center Drive, M/S 15-2-A, Thousand Oaks (California 91320-1789, USA), Fax +1 805 499 75 06, e-mail: ufeige@amgen.com, US aut Campagnuolo G. Department of Pharmacology/Pathology, Amgen, One Amgen Center Drive, M/S 15-2-A, Thousand Oaks (California 91320-1789, USA), Fax +1 805 499 75 06, e-mail: ufeige@amgen.com, US aut Munyakazi L. Department of Biostatistics, Amgen, Thousand Oaks (California 91320-1789, USA), US aut Bolon B. Department of Pharmacology/Pathology, Amgen, One Amgen Center Drive, M/S 15-2-A, Thousand Oaks (California 91320-1789, USA), Fax +1 805 499 75 06, e-mail: ufeige@amgen.com, US aut https://doi.org/10.1007/PL00000629 text/html Onlinezugriff via DOI 1 research-article jats NATIONALLICENCE 856 40 https://doi.org/10.1007/PL00000629 text/html Onlinezugriff via DOI NATIONALLICENCE 700 1- Feige* U. Department of Pharmacology/Pathology, Amgen, One Amgen Center Drive, M/S 15-2-A, Thousand Oaks (California 91320-1789, USA), Fax +1 805 499 75 06, e-mail: ufeige@amgen.com, US aut NATIONALLICENCE 700 1- Hu Y.-L Department of Pharmacology/Pathology, Amgen, One Amgen Center Drive, M/S 15-2-A, Thousand Oaks (California 91320-1789, USA), Fax +1 805 499 75 06, e-mail: ufeige@amgen.com, US aut NATIONALLICENCE 700 1- Gasser J. Department of Pharmacology/Pathology, Amgen, One Amgen Center Drive, M/S 15-2-A, Thousand Oaks (California 91320-1789, USA), Fax +1 805 499 75 06, e-mail: ufeige@amgen.com, US aut NATIONALLICENCE 700 1- Campagnuolo G. Department of Pharmacology/Pathology, Amgen, One Amgen Center Drive, M/S 15-2-A, Thousand Oaks (California 91320-1789, USA), Fax +1 805 499 75 06, e-mail: ufeige@amgen.com, US aut NATIONALLICENCE 700 1- Munyakazi L. Department of Biostatistics, Amgen, Thousand Oaks (California 91320-1789, USA), US aut NATIONALLICENCE 700 1- Bolon B. Department of Pharmacology/Pathology, Amgen, One Amgen Center Drive, M/S 15-2-A, Thousand Oaks (California 91320-1789, USA), Fax +1 805 499 75 06, e-mail: ufeige@amgen.com, US aut Metadata rights reserved Springer special CC-BY-NC licence nationallicence BK010053 XK010053 XK010000 NATIONALLICENCE NATIONALLICENCE NL-springer