<i>Chlamydia pneumoniae</i> infection enhances cellular proliferation and reduces steroid responsiveness of human peripheral blood mononuclear cells via a tumor necrosis factor-α-dependent pathway

다국어 초록 (Multilingual Abstract)

<P>Summary</P><P>Background</P><P>Although epidemiological studies have found an association between <I>Chlamydia pneumoniae</I> infection and severe asthma, the causality and underlying mechanism are largely unknown. We hypothesized that <I>C. pneumoniae</I> infection increases the proliferation and enhances the survival of immune and inflammatory cells, resulting in reduced responsiveness to corticosteroids and suggesting that the underlying mechanism is related to a TNF-α-dependent pathway.</P><P>Methods</P><P>Human peripheral blood mononuclear cells (PBMCs) were cultured <I>in vitro</I> in the presence or absence of <I>C. pneumoniae</I> infection. Responsiveness to corticosteroids was assayed by adding dexamethasone, and the underlying mechanism was investigated by treating cells with infliximab that is a chimeric anti-TNF-α monoclonal antibody. Cellular proliferation and apoptosis was assessed by thymidine uptake and counting apoptotic cells using flow cytometry.</P><P>Results</P><P>Cellular proliferation was significantly higher in <I>C. pneumoniae</I>-infected PBMCs than in uninfected PBMCs, which is more prominent in Th2-dominant microenvironment. The anti-proliferative and pro-apoptotic effect of corticosteroid were significantly reduced in <I>C. pneumoniae</I>-infected PBMCs compared with uninfected PBMCs. The proliferative effect of <I>C. pneumoniae</I> infection and the reduced response to corticosteroid were effectively reversed by blocking the TNF-α pathway at least partially.</P><P>Conclusion</P><P><I>C. pneumoniae</I> infection enhanced the proliferation and survival of immune and inflammatory cells, resulting in steroid resistance. The reversal of these phenomena by the TNF-α inhibitor suggests that TNF-α may play an important role in the induction of steroid dependence or resistance. A TNF-α inhibitor may therefore be a candidate agent for managing steroid-dependent or -resistant severe asthma.</P>