AbstractThe direct and indirect interactions between the nervous system and its transmitters with NK cell cytotoxic functions has been evaluated in the rat by using the neurotoxin capsaicin (8-methyl-N-vanillyl-6-nonenamide). When administered to neonatal rats, capsaicin (50 mg/Kg in 10% ethanol and 10% tween 80 at 2 days of age) interferes with the synthesis and intraneuronal transport of peptides by causing irreversible degeneration of c fiber afferent nerves.Capsaicin treatment resulted in a marked inhibition of NK and ADCC activities both in the spleen and peripheral blood. Inhibition was already evident on day 15 after treatment and persisted until day 90 in the spleen; at this time NK cytotoxicity in the peripheral blood returned to control levels.The inhibitory effect of capsaicin treatment on peripheral blood NK and ADCC activities was associated with changes in NK cell number evaluated as percentage of cells with an LGL morphology and expressing the NK-RP1 cell surface receptor. LGL numbers did not always correlate with the percentage of NK-RP1+cells suggesting that capsaicin may interfere with maturation of lytic effector cells. Overall these results indicate a direct influence of the nervous system on natural immune cytotoxic functions.