Suppression of the acute-phase response as a biological mechanism for the placebo effect.

The idea that inert substances such as sugar pills can have powerful therapeutic effects--the so-called 'placebo effect'--has been widely accepted by most medical researchers since the 1950s. Today there is increasing scepticism about the reality of the placebo effect. This debate has been too simplistic; rather than asking whether or not the placebo effect exists, as researchers have done up to now, we should be more precise, and ask which medical conditions (if any) are placebo-responsive. There is evidence that pain, swelling, stomach ulcers, depression, and anxiety are all placebo-responsive. These conditions have all been linked, to a greater or lesser extent, with activation of the acute-phase response (the innate immune response). The placebo effect may therefore be mediated by alteration of one or more components of the acute-phase response. The candidates for such biochemical mediators would need to alter the synthesis, activation, receptor-binding or signalling mechanisms of inflammation, sickness behaviour and other aspects of innate immunity. This hypothesis is consistent with current data suggesting that placebos work by triggering the release of endorphins. The hypothesis would be falsified if it were found that other medical conditions, not involving the activation of the acute-phase response, were nonetheless alleviated by placebos.