Haloperidol and spiperone potentiate murine splenic B cell proliferation

The neuroleptics haloperidol and spiperone potentiated anti-mu induced murine B-lymphocyte proliferation in vitro and lowered the threshold of anti-mu antibody needed to trigger proliferation. Because haloperidol and spiperone are best known for actions at D2, 5HT2, alpha 1 and sigma (sigma) receptors, a series of agonists and antagonists of these receptors were tested. Dopamine and norepinephrine inhibited, and serotonin (5HT) enhanced B-cell proliferation. Spiperone opposed the suppression of proliferation by dopamine and norepinephrine. However, antagonists of D1, D2, D3, D5, 5HT2, 5HT1A, and alpha 1 receptors did not mimic the effect of haloperidol and spiperone. Furthermore, a series of sigma agonists failed to affect B-cell proliferation. Therefore it is likely that the effects of haloperidol and spiperone are not due to actions at known dopamine, 5HT, alpha 1, or sigma receptors. These findings indicate neuroleptics act not only in the CNS, but also directly on B-lymphocytes of the immune system. The pharmacological site of this action is not clear at this time.