Proinflammatory blood monocytes: main effector and target cells in systemic and renal disease; background and therapeutic implications.

Although peripheral blood monocytes are heterogeneous, they all express the CD14 molecule, a multifunctional receptor, and part of the toll-like membrane receptor complex. In healthy persons, a minor subset (8%) coexpresses CD14 and CD16, a low affinity Fc-gamma type III receptor. This subpopulation shows characteristics of tissue macrophages and expands greatly in acute and chronic infections, systemic inflammatory syndromes, hyperlipidedemia, AIDS and renal failure. CD14+/CD16+ monocytes (Mo) exhibit higher phagocytosis activity than CD14++/CD16-negative monocytes and synthesize high levels of interleukin-1, TNF-alpha and HLA-DR, -DP and -DQ antigens. Glucocorticoids (and interleukin-4), and successful therapy in patients with inflammatory and septic complications lead to a down-regulation in the expression of CD14 and deplete CD14+/CD16+-proinflammatory Mo. Recovery of low monocytic HLA-DR expression parallels clinical improvement. Serial analyses of Mo phenotypes may be useful tools for monitoring patients receiving immunosuppressive and anti-inflammatory therapy respectively.