EFFECTS OF SUBSTANCE-P AND SELECTED OTHER NEUROPEPTIDES ON THE SYNTHESIS OF INTERLEUKIN-1-BETA AND INTERLEUKIN-6 IN HUMAN MONOCYTES - A REEXAMINATION

Recent studies have suggested that substance P (SP) and some other neu ropeptides are able to induce the synthesis of the proinflammatory cyt okines interleukin-l (IL-1) and interleukin-6 (IL-6) in peripheral blo od mononuclear cells. In the present study, we re-examined these findi ngs by using a completely endotoxin-free monocyte cultivation system. We demonstrate that the neuropeptides SP, vasoactive intestinal peptid e, substance K, cholecystokinine, alpha-endorphin, and beta-endorphin are consistently unable to induce the synthesis of IL-1 and IL-6 in hu man peripheral blood monocytes. However, low amounts of LPS (1 pg/ml) synergized with SP to induce IL-6 mRNA expression. In contrast to its lack of effect in monocytes, we were able to confirm the ability of SP to induce cytokine synthesis in astrocytic cells. Our results raise q uestions about previous results claiming a neuropeptide-induced synthe sis of proinflammatory cytokines in human monocytes. In conjunction wi th other studies, we suggest that undetected levels of endotoxin/LPS i n the culture medium may have been primarily responsible for results s uggesting an inductive effect of neuropeptides on cytokine synthesis i n monocytes.