A simple systems approach to neural-immune communication.

The marine mollusc Aplysia californica is emerging as a useful model system to study neuralimmune communication at the mechanistic level because it has a well characterized nervous system that is easily accessible and it shares with mammals similar basic cellular defensive responses to wounded or non-self, i.e. the accumulation of defense cells (haemocytes) at the target site. Loose ligation of peripheral nerves in Aplysia induces a cellular defense response as evidenced by the accumulation of numerous haemocytes around the ligature. The excitability of nociceptive sensory neurons having axons close to the responding haemocytes is significantly increased. Haemocytes also accumulate at regions of axonal injury. The finding that human recombinant IL-1 beta can enhance the expression of injury-induced sensory hyperexcitability coupled with the detection of (ir)IL-1 in Aplysia haemolymph raises the interesting possibility that cytokines released from activated haemocytes attracted to an injured nerve or to a foreign body close to peripheral nerves may modulate nociceptive sensory function. The feasibility of using results from simple system such as Aplysia to formulate testable hypotheses in more complex systems is also discussed.