The chart summarizes the results of a number of simulations, showing the relative effects of reduction in the IL-6 and the IL-1B secretion rates. Green represents IL-1B and red represents IL-6. Up to about 50% reduction, both treatments are comparable. Beyond this level, one sees that targeting IL-1B secretion is more effective for overall neuron health than IL-6. If secretion is decreased by 60%, after 300 minutes, the overall neuron health for the IL-1B reduction is relatively good (74% of normal), and certainly much better than overall neuron health for the IL-6 reduction (3% of normal). This preliminary result indicates that IL-1B is a higher priority target than IL-6.

More details can be gleaned from viewing the simulations as they evolve. For example, reduced IL-1B secretion by microglia delays invasion of a region by astrocytes. This then delays the release of IL-6 which is directly related to neuronal stressing and death. Once astrocytes enter the region, neurons deteriorate at a relatively fixed rate. (The lines in the graph below have the same slope when neurons start to be stressed.)

Decreasing the IL-6 secretion rate of astrocytes has a distinct effect: it actually slows down the rate of decline in neuron health (lines in the graph below eventually change slope as the secretion rate is reduced). It takes longer for a fatal dose of IL-6 to be attained for reduced IL-6 secretion rates.

Although the results are preliminary, the simulations show what factors could be important. Apart from targeting secretion rates of the interleukins, one could consider several similar parameters that may have related overall effects: (1) Absorption of IL-1B by the neurons: As neurons absorb IL-1B, they also prevent its spread and induction of the astrocyte invasion which eventually causes death. (2) The rate of absorption of IL-6 by neurons: if this is reduced, buildup of a toxic level of IL-6 would also be delayed. This suggests IL-6 agonists that would compete with IL-6 for binding sites.

Our current values for both IL-1B and IL-6 absorption by neurons are speculative and require calibration and validation. Results will become more realistic, and on a firmer footing once absorption rates by neurons are calibrated accurately. (Since these values are parameters in our simulation, they are easily updated - whether in house or by potential users - as new information is obtained.)

The simulation is an emerging, potentially powerful tool that allows targeting different factors to investigate their possible effects. It also enables one to see what changes as new pieces of the entire process are included. The simulation is updated easily. This allows the user to make important discoveries by changing parameter values, and allows us to add more details as more processes become better understood.