Re-educating immune cells
20 May 2008
Macrophages are large white blood cells that produce inflammatory proteins that attack foreign bodies such as invading organisms or tumour cells. However, in certain cases macrophages appear to be ineffective, with their ability to fight infection and kill tumour cells suppressed. Until now, it was not understood what caused this effect.
Research carried out at Imperial College London has identified a key protein known as IKKβ which is involved in determining the macrophages' ability to attack tumour cells and fight infection. By inhibiting IKKβ, the researchers were able to 're-educate' macrophages so that they behave in the classical way, as a vital part of the body's immune response. The results of the study, part-funded by the Wellcome Trust, are published today in the ‘Journal of Experimental Medicine’.
Dr Toby Lawrence, now at Queen Mary's University London (QMUL) and who led the study, believes that as well as providing valuable insights into how to boost immunity in infection, the findings may have important implications for current drug developments for the treatment of chronic inflammatory diseases, such as rheumatoid arthritis. Because the role of IKKβ differs depending on the context, inhibiting its action may lead to an increase or decrease in inflammatory proteins depending on the role of macrophages in the disease.
"Many big pharmaceutical companies have advanced programmes to develop IKKβ inhibitors, focusing on chronic inflammatory diseases," says Dr Lawrence. "Our research indicates that in chronic inflammatory diseases, inhibiting IKKβ may lead to more inflammation, causing adverse effects. In other infections, however, an inflammatory response is how our body fights back."
In a parallel study, also published today in the same journal, a second team at QMUL, led by Dr Thorsten Hagemann, has found that IKKβ can play a similar role in blocking the ability of macrophages to fight tumour cells.
Dr Lawrence believes that understanding how pathogenic organisms and cancer cells have evolved to manipulate IKKβ and protect themselves from attack by the immune system will provide clues on how to boost immunity in infection and cancer.
Image: Macrophage with phagocytic vesicle (pink) and lysosomes (dark red); University of Edinburgh, Wellcome Images