Fionula Brennan

Fionula Brennan (1957–2012) was an Irish immunologist and Professor of Cytokine Immunopathology at the Kennedy Institute of Rheumatology.[1]

Fionula Brennan
Born1957
Manorhamilton, Ireland
Died15 June 2012(2012-06-15) (aged 54–55)
Alma mater
Known forDiscovering "TNF-dependent cytokine cascade", the anti-TNF mechanism affecting rheumatoid arthritis
Scientific career
FieldsImmunology
Institutions

Brennan described the role of tumour necrosis factor (TNF) in rheumatoid arthritis by demonstrating that anti-TNF antibodies inhibit inflammation of the synovial joints. This research led directly to the development of anti-TNF therapy.[2]

Early life and education

Fionula Brennan was born in Manorhamilton, County Leitrim, to Josie and Ted Brennan in 1957. She had a brother and a sister.[3]

Brennan received her undergraduate degree and PhD in immunology from the University of Bristol.[1]

Career

From the late 1980s, Brennan worked at the Kennedy Institute of Rheumatology, where her work enabled revolutions in the treatment of rheumatoid arthritis.[4] Brennan was Professor of Cytokine Immunopathology at the Kennedy Institute of Rheumatology until 2011.[5]

In the late 1980s, developments in knowledge about cytokine production and methods of study had made it possible to investigate further their role in rheumatoid arthritis. Since it remained unclear which cytokine should be targeted to produce therapeutic effects, they were not investigated as therapeutic targets.[6] However, as a postdoctoral researcher working initially with Ravinder Maini and then under Marc Feldmann from 1988 to 1989, Brennan questioned whether it was possible to suppress pathologic TNF selectively.[7] Her work developed upon that of Feldmann and Glenn Buchan.

Brennan's experiments analysed cytokine expression in a dissociated synovial cell culture model, which kept immune/inflammatory cells alive and made it possible to study disregulation.[6][8]

Brennan's experiments provided the first evidence that TNF might be a therapeutic target.[9][10] Brennan's work showed that rheumatoid mixed synovial cell cultures were distinct from osteoarthritic cell cultures because anti-TNF antibodies reduced production of IL-1 cytokines, which regulate immune and inflammatory responses.[9] Later experiments showed that it also downregulated other proinflammatory cytokines (GM-CSF, IL-6, and IL-8). This unexpected "TNF-dependent cytokine cascade" suggested that TNF might be a therapeutic target for rheumatoid arthritis.[6][11][12]

Brennan spent the rest of her career building upon her significant early findings the importance of TNF overproduction in rheumatoid arthritis. She challenged the idea that T-cells were not relevant to rheumatoid arthritis by showing that TNF was produced by T-cell activated macrophages.[1]

Brennan's final project sought to understand why regulatory T-cells failed to affect disease process. She found that pathogenic T-cells in joints and cytokine activated T-cells were not controlled by regulatory T-cells.[1]

Research community

Brennan and Frances Balkwill ran the British Cytokine Group (BCG) for around 10 years. This group developed out of the 1987 TNF meeting and brought together researchers that worked in different fields such as cancer research and infections and inflammatory disease.[8]

Death and legacy

Brennan died on 15 June 2012 at Parkside Hospital, Wimbledon, as a result of cancer. She was survived by her husband Paul Gallagher and children Ciarán and Bridget.[13]

The Marc and Tania Feldmann Charitable Trust plan to commemorate Brennan by naming a grant in her honour.[14]

References
  1. Feldmann, Marc (2013). Fionula Brennan's career: Analysis of dysregulation of TNF in pathogenesis of rheumatoid arthritis and its present and future therapeutic implications (PDF). 14th International TNF Conference (TNF2013). Québec.
  2. Dalbeth, Nicola; Neogi, Tuhina (2022-02-03). "Where are the women 'Heroes and Pillars of Rheumatology'?". Annals of the Rheumatic Diseases. doi:10.1136/annrheumdis-2021-222047. ISSN 0003-4967. PMID 35121589. S2CID 246556433.
  3. "Fionula will be sadly missed". Independent.ie. 23 July 2012. Retrieved 1 February 2023.
  4. Ruddle, Nancy H. (April 2014). "Lymphotoxin and TNF: How it all began—A tribute to the travelers". Cytokine & Growth Factor Reviews. 25 (2): 83–89. doi:10.1016/j.cytogfr.2014.02.001. PMC 4027955. PMID 24636534.
  5. "Impact case study (REF3b): Threefold Increase in the Use of Anti-TNF in the Treatment of Common Chronic Inflammatory Conditions". REF 2014 Submission. Imperial College London. 2014.
  6. Udalova, Irina; Monaco, Claudia; Nanchahal, Jagdeep; Feldmann, Marc (2016-08-12). Gordon, Siamon (ed.). "Anti-TNF Therapy". Microbiology Spectrum. 4 (4): 4.4.46. doi:10.1128/microbiolspec.MCHD-0022-2015. ISSN 2165-0497. PMID 27726761.
  7. Wollheim, Frank A. (2001-08-06). "Advances in Targeted Therapies III, Nassau, Bahamas, 27 April-1 May 2001". Arthritis Research & Therapy. 3 (5): E005. doi:10.1186/ar323. ISSN 1478-6362. PMC 128906.
  8. Zarros, A; Jones, E M; Tansey, E M (2015). The Recent History of Tumour Necrosis Factor (TNF) (PDF). Witness Seminar held by the History of Modern Biomedicine Research Group, Queen Mary University of London. Retrieved 1 February 2023.
  9. Feldmann, Marc (2009-04-01). "Translating Molecular Insights in Autoimmunity into Effective Therapy". Annual Review of Immunology. 27 (1): 1–27. doi:10.1146/annurev-immunol-082708-100732. ISSN 0732-0582. PMID 19007330.
  10. Feldmann, Marc; Brennan, Fionula M; Williams, Richard O; Woody, James N; Maini, Ravinder N (February 2004). "The transfer of a laboratory based hypothesis to a clinically useful therapy: the development of anti-TNF therapy of rheumatoid arthritis". Best Practice & Research Clinical Rheumatology. 18 (1): 59–80. doi:10.1016/j.berh.2003.09.010. PMID 15123038.
  11. Malaviya, Anand N; Mehra, Narinder K (2018). "A fascinating story of the discovery & development of biologicals for use in clinical medicine". Indian Journal of Medical Research. 148 (3): 263–278. doi:10.4103/ijmr.IJMR_1471_18. ISSN 0971-5916. PMC 6251261. PMID 30425216.
  12. "Our History". The Kennedy Institute of Rheumatology. Retrieved 2023-02-01.
  13. "BRENNAN, Professor Fionula : Death". The Irish Times. June 2012.
  14. "Marc & Tania Feldmann Charitable Trust Annual Report and Unaudited Financial Statements, year ending April 2020". charitycommission.gov.uk. Retrieved 1 March 2023.
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