What if cases of delirium or instances of delusions were only a symptom of an imbalance of inflammatory growth factors in your brain? What if the root cause for debilitating mental diseases, such as Alzheimer’s, were really grounded in the never-ending tug and pull balancing act between cytokines and chemokines, their receptors and their inhibitors that goes on inside each of us every day? What if the whole of “getting older” (the joint pain, the memory lapses, etc.) was just a side effect of the messed up secretions of interleukins, fibroblast growth factors (FGFs), and other growth factors that we unknowingly depend on without even knowing what for? Those are some of the questions which motivated Dunja Westhoff and colleagues from the University of Amsterdam to try to find out.

esthoff and her group decided to look into the pre-operative expression pattern of cytokines in elderly patients who were admitted for hip fracture. A large percentage of elderly patients with hip fractures suffer from post-operative delirium, which seems to make sense since both the fracture and the surgery lead to systemic responses. Of course, discovering the subtleties of cytokine expression in elderly patients is no walk in the park. They were unable to detect 5 cytokines at all and 21 other cytokines were only detectable in a minority of the patients…leaving just 22 growth factors (including FGF2, IL1B, IL2, IL3, IL4, IL6, TNF-α, and EGF) that could be measured across both patients suffering from delirium and those who did not.

They eventually focused on 4 cytokines, three that had significantly lower levels (Flt-3L, IL1RA, and IL6) and one that was significantly higher (IP-10) in post-operative delirious patients. IL1RA (also listed as IL1RN) is a natural inhibitor of IL1A and IL1B, which are both pro-inflammatory cytokines in the brain. Subsequently, the reduction of IL1RA would lead to higher inflammation in the brain. Decreased levels of IL1RA have also been previously observed in patients suffering from either Alzheimer’s or rheumatoid arthritis.

This is a small study, and knowingly limited in its findings. But there seems to be a spark of truth amongst the clutter of results. Westhoff’s results seem to agree that there is a neuroinflammatory response effect which may be at least partially responsible for cases of delirium. Consequently, this may become an exciting avenue of clinical study and research. More research is necessary in order to prove if the effect is due to heightened proinflammatory responses or reduced anti-inflammatory responses. As usual, we have so much yet to learn. But, if true, this should lead to some exciting breakthroughs!

Westhoff, D., et al. (2013). “Preoperative cerebrospinal fluid cytokine levels and the risk of postoperative delirium in elderly hip fracture patients.” J Neuroinflammation 10(1): 122.

Category Code: 79101