Endogenous NGF regulates CGRP expression in human monocytes, and affects HLA-DR and CD86 expression and IL-10 production.

Our recent results on autocrine nerve growth factor (NGF) synthesis in B lymphocytes, which directly regulates the expression and release of calcitonin gene-related peptide (CGRP), a neuropeptide known to down-regulate immune response, led us to propose an anti-inflammatory action of NGF. In the present work, we investigated whether the endogenous synthesis of NGF can regulate the expression of CGRP in other antigen-presenting cells, such as monocytes, and whether this may have a functional effect. Our data indicate that human monocytes synthesize basal levels of NGF and CGRP and that, following lipopolysaccharide (LPS) stimulation, NGF and CGRP expression are both up-regulated. When endogenous NGF is neutralized, the up-regulation of CGRP expression induced by LPS is inhibited. The expression of membrane molecules involved in T-cell activation such as human leukocyte antigen-DR (HLA-DR) and CD86 is affected by endogenous NGF, and similar effects were obtained using a CGRP(1) receptor antagonist. In addition, NGF deprivation in LPS-treated monocytes significantly decreases interleukin 10 (IL-10) synthesis. Our findings indicate that endogenous NGF synthesis has a functional role and may represent a physiologic mechanism to down-regulate major histocompatibility complex (MHC) class II and CD86 expression and alter the development of immune responses.