Malaria continues to be the dominant infectious disease in the tropical world, and, with increasing resistance to antimalarial drugs, is a significant cause of illness and death in returning travellers. Moreover, it is a disease that continues to serve as a useful model to understand our understanding of systemic infectious states in general, including influenza and sepsis. We have continued to develop our concept, which now has wide acceptance in malaria, influenza and sepsis, that the harm caused by these diseases is not the direct effect of the infectious agents, but the consequence of inflammatory cytokines released from the patient’s own cells.
Influenza, again newsworthy because of the evolution of a bird strain (H5N1) that has a high mortality in people, could evolve further to spread readily from human to human. Thus it is an urgent target for applying knowledge gleaned from the cytokine approach to disease. We have recently published that an agent, already in human use for another purpose, and known to inhibit inflammatory cytokine generation, reduces mortality in influenza-infected mice. A major focus of our work is to expand these studies, and Lisa Alleva and I are currently funded for this purpose. |
Yasumi Endoh, Yuen Ming Chung, Ian A. Clark, Carolyn L. Geczy and Kenneth Hsu (2009) IL-10-Dependent S100A8 Gene Induction in Monocytes/Macrophages by Double-Stranded RNA1 . The Journal of Immunology, 182: 2258-2268.
Alleva LM, Cai C and Clark IA. Using complementary and alternative medicines to target the host response during severe influenza (2009). Evidence-based Complementary and Alternative Medicine (accepted 30.08.09).
Clark IA, Alleva LM. Is human malarial coma caused, or merely deepened, by sequestration? Trends Parasitol. (2009) 25:314-318.
Clark IA, Alleva LM. Invited commentary on David Fedson's article “Confronting the next influenza pandemic with anti-inflammatory and immuno-modulatory agents: why they are needed and how they might work” (2009). Influenza Other Respi. Viruses 3:199-201.
Clark, I.A. Along a TNF-paved road from dead parasites in red cells to cerebral malaria, and beyond. Parasitology, 136: 1457-1468.
Clark, I. A., Alleva, L. M., Budd, A., and Cowden, W. B. (2008) Understanding the role of inflammatory cytokines in malaria and related diseases. Tropical Medicine and Infectious Disease, 6: 67-81.
Alleva, L. M., Budd, A. and Clark, I. A (2008) Systemic release of high mobility group box 1 protein during severe murine influenza. Journal of Immunology 181: 1454-1459.
Budd, A., Alleva, L. M., Alsharifi, M., Koskinen, A., Smythe, V., Müllbacher, A., Wood, J. and Clark, I. A. (2007) Increased survival after gemfibrozil treatment of severe mouse influenza. Antimicrobial Agents and Chemotherapy 51, 2965-2968.
Clark, I. A. (2007). How TNF was recognized to be a key mechanism of disease. Cytokine and Growth Factor Reviews 18: 335-343.
Clark, I. A. (2007) The advent of the cytokine storm. Immunology and Cell Biology 85:271-273.
Clark, I. A. and Griffiths, M. J. The Molecular Basis of Paediatric Malarial Disease. In
Pediatric Infectious Diseases Revisited. Birkhauser, Basel. H. Schroten and S. Wirth (eds), 2007, pp. 239-272.
Clark, I. A., Budd, A. C., Alleva, L. M. and Cowden, W. B. (2006). Human malarial disease: a consequence of inflammatory cytokine release. Malaria Journal, 5, 85. (on-line publication, 33 pages)
Alleva, L. M.,Yang, H., Tracey, K. J. and Clark, I. A. (2005) High mobility group box 1 (HMGB1) protein: possible amplification signal in the pathogenesis of falciparum malaria. Transactions of the Royal Society of Tropical Medicine and Hygiene, 99:171-174.
Clark, I. A., Alleva, L. M., Mills, A. C., and Cowden W. B. (2004) Disease pathogenesis in malaria and clinically similar conditions. Clinical Microbiol. Reviews, 17:509-539 |
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