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 mac rophages 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 mu g/footpad) and then decline d. SOM expression after LPS injection reached a maximum at 5-7 days. Stimul ation of thioglycolate-elicited peritoneal macrophages with LPS (20 mu g/ml ), recombinant interferon-gamma (rIFN-gamma, 100 U/ml), and LPS plus rIFN-g amma induced SOM and SP. Thioglycolate-elicited, unstimulated peritoneal ma crophages also synthesized these peptides, SOM (10(-12)-10(-8) M) Significa ntly inhibited IL-6 and IFN-gamma production, whereas SP at those concentra tions enhanced cytokine production by activated lymphocytes and macrophages . These findings suggest that neuropeptides which originate from macrophage s and nerve fibers act as immunomodulators to mediate changes in the patter n of cytokine production. Copyright (C) 2000 S. Karger AG, Basel.