Somatostatin and substance P induced in vivo by lipopolysaccharide and in peritoneal macrophages stimulated with lipopolysaccharide or interferon- gamma have differential effects on murine cytokine production

We have investigated whether lipopolysaccharide (LPS) induces substance P (SP) and somatostatin (SOM) in popliteal lymph nodes in vivo and whether macrophages are a source of SP and SOM in vitro. We have also investigated the effect of SP and SOM treatment on the production of cytokines. SP reached a maximum 3 days after injection of LPS (100 μg/footpad) and then declined. SOM expression after LPS injection reached a maximum at 5-7 days. Stimulation of thioglycolate-elicited peritoneal macrophages with LPS (20 μg/ml), recombinant interferon-γ (rIFN-γ, 100 U/ml), and LPS plus rIFN-γ induced SOM and SP. Thioglycolate-elicited, unstimulated peritoneal macrophages also synthesized these peptides. SOM (10^-12-10^-8 M) significantly inhibited IL-6 and IFN-γ production, whereas SP at those concentrations enhanced cytokine production by activated lymphocytes and macrophages. These findings suggest that neuro-peptides which originate from macrophages and nerve fibers act as immunomodulators to mediate changes in the pattern of cytokine production. Copyright(C) 2000 S. Karger AG, Basel.