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Temporal cytokine expression and the target organ attributes unravel novel aspects of autoimmune arthritis.

Astry B, Venkatesha SH, Moudgil KD - Indian J. Med. Res. (2013)

Bottom Line: Further, various inhibitors of angiogenesis are effective in suppressing arthritis.Taken together, the differential cytokine responses and unique attributes of the target organ have revealed novel aspects of disease susceptibility and joint damage in AA.The translation of this basic research in animal models to RA patients would not only advance our understanding of the disease process, but also offer novel avenues for immunomodulation of this disease.

View Article: PubMed Central - PubMed

Affiliation: Department of Microbiology & Immunology, University of Maryland School of Medicine, Baltimore, MD, USA.

ABSTRACT
Susceptibility to autoimmunity is determined by multiple factors. Defining the contribution of the quantitative versus qualitative aspects of antigen-directed immune responses as well as the factors influencing target organ susceptibility is vital to advancing the understanding of the pathogenesis of autoimmunity. In a series of studies, we have addressed these issues using the adjuvant-induced arthritis (AA) model of human rheumatoid arthritis (RA). Lewis rats are susceptible to AA following immunization with heat-killed Mycobacterium tuberculosis H37Ra, whereas Wistar-Kyoto (WKY) rats of the same MHC (major histocompatibility complex) haplotype are resistant. Comparative studies on these and other susceptible/resistant rodent strains have offered interesting insights into differential cytokine responses in the face of comparable T cell proliferative response to the disease relevant antigens. Study of the cytokine kinetics have also permitted validation of the disease-protective versus disease-aggravating effects of specific cytokines by treatment of rats/mice with those cytokines at different phases of the disease. In regard to the target organ attributes, the migration of arthritogenic leukocytes into the joints; the expression of mediators of inflammation, angiogenesis, and tissue damage; the role of vascular permeability; and the characteristics of vascular endothelial cells have been examined. Further, various inhibitors of angiogenesis are effective in suppressing arthritis. Taken together, the differential cytokine responses and unique attributes of the target organ have revealed novel aspects of disease susceptibility and joint damage in AA. The translation of this basic research in animal models to RA patients would not only advance our understanding of the disease process, but also offer novel avenues for immunomodulation of this disease.

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The dynamics of cytokine expression during the course of adjuvant arthritis. Adjuvant arthritis (AA) in the Lewis rat, induced following immunization with heat-killed M. tuberculosis H37Ra, displays distinct phases of the disease. These phases include incubation, onset, peak and regression. Proinflammatory cytokines play a vital role in the initiation and progression of arthritis, whereas anti-inflammatory cytokines facilitate regression of inflammatory arthritis. The levels of cytokines represented by the number of triangles are relative to each phase for that particular cytokine. (IL, interleukin; IFN, interferon; TNF, tumour necrosis factor).Source: Refs 22, 23, 27, 65, 66
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Figure 2: The dynamics of cytokine expression during the course of adjuvant arthritis. Adjuvant arthritis (AA) in the Lewis rat, induced following immunization with heat-killed M. tuberculosis H37Ra, displays distinct phases of the disease. These phases include incubation, onset, peak and regression. Proinflammatory cytokines play a vital role in the initiation and progression of arthritis, whereas anti-inflammatory cytokines facilitate regression of inflammatory arthritis. The levels of cytokines represented by the number of triangles are relative to each phase for that particular cytokine. (IL, interleukin; IFN, interferon; TNF, tumour necrosis factor).Source: Refs 22, 23, 27, 65, 66

Mentions: Animal models of human RA29 permit comprehensive experimental studies on the pathogenesis of autoimmunity, including the role of T cells and cytokines in the disease process. Two of the commonly used models of RA are adjuvant arthritis (AA) in rats7 and collagen-induced arthritis (CIA) in mice/rats64. The cytokines released during the course of autoimmune arthritis influence the severity of the pathological and clinical features of the disease (Figs 1 and 2). The AA model system has extensively been used to examine the disease-related events at different time points in the course of the disease as well as for testing potential anti-arthritic agents for their therapeutic efficacy and side effects. However, not all rat strains are equally susceptible to autoimmune arthritis. The Lewis rat is highly susceptible to AA, whereas the Wistar-Kyoto (WKY) rat is resistant to arthritis despite having a similar major histocompatibility complex (MHC) haplotype as the Lewis rat51121. WKY rats provide a good control for Lewis rats for studies on disease pathogenesis. In our studies, we have exploited this pair of rat strains for addressing important aspects of AA, for example, epitope mapping of the disease-related antigen Bhsp65511 , cellular migration into the joints67 , the dynamics and epitope reactivity of antibodies produced during AA68 , and cytokine responses against Bhsp6522232769.


Temporal cytokine expression and the target organ attributes unravel novel aspects of autoimmune arthritis.

Astry B, Venkatesha SH, Moudgil KD - Indian J. Med. Res. (2013)

The dynamics of cytokine expression during the course of adjuvant arthritis. Adjuvant arthritis (AA) in the Lewis rat, induced following immunization with heat-killed M. tuberculosis H37Ra, displays distinct phases of the disease. These phases include incubation, onset, peak and regression. Proinflammatory cytokines play a vital role in the initiation and progression of arthritis, whereas anti-inflammatory cytokines facilitate regression of inflammatory arthritis. The levels of cytokines represented by the number of triangles are relative to each phase for that particular cytokine. (IL, interleukin; IFN, interferon; TNF, tumour necrosis factor).Source: Refs 22, 23, 27, 65, 66
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC3928702&req=5

Figure 2: The dynamics of cytokine expression during the course of adjuvant arthritis. Adjuvant arthritis (AA) in the Lewis rat, induced following immunization with heat-killed M. tuberculosis H37Ra, displays distinct phases of the disease. These phases include incubation, onset, peak and regression. Proinflammatory cytokines play a vital role in the initiation and progression of arthritis, whereas anti-inflammatory cytokines facilitate regression of inflammatory arthritis. The levels of cytokines represented by the number of triangles are relative to each phase for that particular cytokine. (IL, interleukin; IFN, interferon; TNF, tumour necrosis factor).Source: Refs 22, 23, 27, 65, 66
Mentions: Animal models of human RA29 permit comprehensive experimental studies on the pathogenesis of autoimmunity, including the role of T cells and cytokines in the disease process. Two of the commonly used models of RA are adjuvant arthritis (AA) in rats7 and collagen-induced arthritis (CIA) in mice/rats64. The cytokines released during the course of autoimmune arthritis influence the severity of the pathological and clinical features of the disease (Figs 1 and 2). The AA model system has extensively been used to examine the disease-related events at different time points in the course of the disease as well as for testing potential anti-arthritic agents for their therapeutic efficacy and side effects. However, not all rat strains are equally susceptible to autoimmune arthritis. The Lewis rat is highly susceptible to AA, whereas the Wistar-Kyoto (WKY) rat is resistant to arthritis despite having a similar major histocompatibility complex (MHC) haplotype as the Lewis rat51121. WKY rats provide a good control for Lewis rats for studies on disease pathogenesis. In our studies, we have exploited this pair of rat strains for addressing important aspects of AA, for example, epitope mapping of the disease-related antigen Bhsp65511 , cellular migration into the joints67 , the dynamics and epitope reactivity of antibodies produced during AA68 , and cytokine responses against Bhsp6522232769.

Bottom Line: Further, various inhibitors of angiogenesis are effective in suppressing arthritis.Taken together, the differential cytokine responses and unique attributes of the target organ have revealed novel aspects of disease susceptibility and joint damage in AA.The translation of this basic research in animal models to RA patients would not only advance our understanding of the disease process, but also offer novel avenues for immunomodulation of this disease.

View Article: PubMed Central - PubMed

Affiliation: Department of Microbiology & Immunology, University of Maryland School of Medicine, Baltimore, MD, USA.

ABSTRACT
Susceptibility to autoimmunity is determined by multiple factors. Defining the contribution of the quantitative versus qualitative aspects of antigen-directed immune responses as well as the factors influencing target organ susceptibility is vital to advancing the understanding of the pathogenesis of autoimmunity. In a series of studies, we have addressed these issues using the adjuvant-induced arthritis (AA) model of human rheumatoid arthritis (RA). Lewis rats are susceptible to AA following immunization with heat-killed Mycobacterium tuberculosis H37Ra, whereas Wistar-Kyoto (WKY) rats of the same MHC (major histocompatibility complex) haplotype are resistant. Comparative studies on these and other susceptible/resistant rodent strains have offered interesting insights into differential cytokine responses in the face of comparable T cell proliferative response to the disease relevant antigens. Study of the cytokine kinetics have also permitted validation of the disease-protective versus disease-aggravating effects of specific cytokines by treatment of rats/mice with those cytokines at different phases of the disease. In regard to the target organ attributes, the migration of arthritogenic leukocytes into the joints; the expression of mediators of inflammation, angiogenesis, and tissue damage; the role of vascular permeability; and the characteristics of vascular endothelial cells have been examined. Further, various inhibitors of angiogenesis are effective in suppressing arthritis. Taken together, the differential cytokine responses and unique attributes of the target organ have revealed novel aspects of disease susceptibility and joint damage in AA. The translation of this basic research in animal models to RA patients would not only advance our understanding of the disease process, but also offer novel avenues for immunomodulation of this disease.

Show MeSH
Related in: MedlinePlus