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. 1999 Jul;58(7):428–434. doi: 10.1136/ard.58.7.428

Anti-inflammatory effects of systemic anti-tumour necrosis factor α treatment in human/murine SCID arthritis

H Schadlich 1, J Ermann 1, M Biskop 1, W Falk 1, F Sperling 1, A Jungel 1, J Lehmann 1, F Emmrich 1, U Sack 1
PMCID: PMC1752912  PMID: 10381487

Abstract

OBJECTIVES—To evaluate in vivo the contribution of tumour necrosis factor α (TNFα) to the chimeric transfer model of human rheumatoid arthritis synovial membrane into SCID mice (hu/mu SCID arthritis), systemic anti-TNFα treatment was performed and the clinical, serological, and histopathological effects of this treatment assessed.
METHODS—Animals were treated with the rat-antimouse TNFα monoclonal antibody V1q, starting on day 1 after hu/mu engraftment, twice weekly for 12 weeks. Joint swelling, serum concentrations of human and murine interleukin 6 (IL6), and serum amyloid P (SAP) were measured. Histopathological and immunohistochemical analyses of the joints were also performed at the end of treatment.
RESULTS—Neutralisation of murine TNFα induced the following effects: (a) reduction of extent and duration of the acute arthritis phase, with significant reduction of joint swelling at two weeks; (b) decrease of murine SAP concentrations after the first antibody administration; and (c) increase of murine IL6 in the serum. At the end of treatment, there was a significant reduction of the inflammatory infiltration in the engrafted joints. Because of the mild degree of joint erosion, no treatment effects could be demonstrated on the destructive process.
CONCLUSION—In the lymphocyte independent hu/mu SCID arthritis, anti-TNFα treatment reduces local and systemic signs of inflammation.



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Figure 1  .

Figure 1  

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Immunohistochemical staining for (A) murine TNFα, original magnification × 160, and (B) murine IL6, original magnification × 160, in the knee joint of SCID mice after transplantation of human RA-SM. Cytokine producing cells are stained brown (AEC) and are indicated by arrows. (C) Isotype control (purified rat IgG1, κ), original magnification × 160.    

Figure 2  .

Figure 2  

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Joint thickness measurement of left and right knee of SCID mice after transplantation of RA-SM I (see table 1 for details) and intraperitoneal application of 120 µg anti-murine TNFα MoAb twice a week (A: engrafted knee, B: contralateral knee); or after transplantation of RA-SM II (see table 1 for details) and intraperitoneal application of 300 µg monoclonal anti-murine TNFα monoclonal antibody twice a week (C: engrafted knee, D: contralateral knee). The appropriate controls are also shown (treatment with isotype antibody; no treatment; and treatment of sham operated mice). Significant changes are indicated.

Figure 3  .

Figure 3  

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Serum concentrations of murine IL6 (A) and murine SAP (B) after implantation of RA-SM II (see table 1 for details) and administration of 300 µg anti-murine TNFα monoclonal antibody as indicated by arrowheads. The appropriate controls are also shown. p<0.05 in the comparison between anti-TNF treatment and untreated hu/mu SCID.

Figure 4  .

Figure 4  

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Giemsa staining of cryostat joint section eight weeks after implantation of RA-SM I and (A) treatment with 120 µg of anti-murine TNFα antibody twice weekly or (B) isotype control, original magnification × 100. Anti-TNF treatment significantly reduces infiltration of synovial membrane and joint space by murine inflammatory cells, mainly macrophages.             

Figure 5  .

Figure 5  

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Histological scoring of joint sections eight weeks after implantation of RA-SM I and treatment with anti-murine TNFα (see methods for details). Values are means (SD), * p < 0.05 for the comparisons indicated by the bars.

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