Effect of macrolides on the expression of human leukocyte antigen-DR and costimulatory molecules on cultured human mononuclear cells

Abstract

Although the clinical effectiveness of long-term low-dose administration of macrolides for diffuse pan- bronchiolitis, sinobronchial syndrome, chronic sinusitis and otitis media with effusion has been well documented, the mechanism of action remains to be determined. To clarify the effect of macrolides on the initiation of immune responses, we investigated changes in the expression levels of human leukocyte antigen (HLA)-DR, a major histocompatibility complex class II antigen, and of costimulatory molecules, such as CD54, CD80 and CD86, on monocytes following administration of macrolides. The expression of HLA-DR, CD54, CD80 and CD86 on cultured human peripheral mononuclear cells following stimulation by interferon (IFN)-γ and lipopolysaccharides (LPS) was analyzed using flow cytometry in the presence and absence of macrolides. The macrolides tested inhibited the expression of CD54, CD80 and CD86 on cultured monocytes following stimulation by IFN-γ and LPS, while the expression of HLA-DR on monocytes was not affected. Suppression of CD80 expression was the most significant among the costimulatory molecules tested and occurred in a dose-dependent manner. These results suggest that macrolides may downregulate the expression levels of costimulatory molecules, such as CD80, and may normalize the hyperimmune responses that may be responsible for the chronic intractable inflammation.