C-REACTIVE PROTEIN INCREASES PRODUCTION OF IL-1-ALPHA, IL-1-BETA, ANDTNF-ALPHA, AND EXPRESSION OF MESSENGER-RNA BY HUMAN ALVEOLAR MACROPHAGES

The concentration of C-reactive protein (CRP) increases in human plasm a up to a thousandfold during inflammatory states. Because tissue macr ophages have been shown to have receptors for CRP, the question arises of whether these cells may respond to increased local concentrations of CRP by producing cytokines capable of participating in the inflamma tory response. Accordingly, we examined the capacity of alveolar macro phages-relatively accessible human macrophages-to produce interleukin- 1 (IL-1) and tumor necrosis factor alpha (TNF-alpha) in response to CR P. We found that production of IL-1alpha, IL-1beta, and TNF-alpha, as measured by bioassay and immunoassay, increased in a dose-dependent ma nner after stimulation by CRP and that the levels of the respective mR NAs analyzed by Northern blot increased proportionally. These findings suggest that one of the functions of CRP may be to stimulate the prod uction of IL-1 and TNF by macrophages at inflammatory sites where alte rations of capillary permeability combined with an increased serum lev el lead to enhanced local concentrations of this acute-phase protein.