Endocrine Abstracts

One of the most important but as yet unanswered questions in inflammation research is not why chronic inflammation occurs but why is does not resolve. Current models of inflammation stress the role of antigen-specific lymphocyte responses and attempt to address the causative agent. However recent studies have begun to challenge the primacy of the lymphocyte and have begun to focus on an extended immune system in which stromal cells, such as macrophages and fibroblasts play a role in the persistence of the inflammatory lesion. In this lecture I will illustrate how fibroblasts play an important role in regulating the switch from acute resolving to chronic persistent inflammation associated with the pathology of diseases such as rheumatoid arthritis¹. In chronic inflammation the normal physiological process of the death and emigration of unwanted inflammatory effector cells becomes disordered leading to accumulation of leucocytes^2–4 within lymphoid aggregates that resemble those seen in lymphoid tissue⁵. I will describe how fibroblasts provide survival and retention signals for leucocytes leading to their inappropriate and persistent accumulation within inflamed tissue⁶. Our work suggests that targeting the stromal microenvironment is likely to be an important strategy for future anti-inflammatory therapies⁷.

References

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2. Salmon M et al. J Clin Invest 1997 99 439–4462.

3. Buckley CD et al. J Immunol 2000 165 3423–3429.

4. Buckley CD Rheumatology 2003 42 1433–44.

5. Amft N et al. Arthritis Rheum 2001 44 2633–41.

6. Parsonage G et al. Thromb Haemost 2003 90 688–97.

7. Filer AD et al. Curr Opin Pharmacol 2006 6 393–400. Epub 2006 May 8.