Altered accessory cell function of alveolar macrophages: a possible mechanism for induction of Th2 secretory profile in idiopathic pulmonary fibrosis

Alveolar macrophages (AMs) are considered to play a central role in the pathogenesis of idiopathic pulmonary fibrosis (IPF). Recent studies have revealed a predominance of the type-2 T-helper (Th2) cytokine pattern of inflammatory response in the pulmonary interstitium in IPF. The aim of the present study was to determine whether or not the altered accessory cell function of AMs could account for the Th2 pattern of chronic inflammation in IPF. The levels of various cytokines were measured in the supernatants of soluble anti-CD3 monoclonal antibody (MoAb)-stimulated T-cells, co-cultured with autologous AMs, by enzyme-linked immunosorbent assay (ELISA). Cells from six patients with IPF and from nine normal volunteers (five nonsmokers and four smokers) were examined. The inhibitory effect of interleukin (IL)-10 on the accessory cell function of AMs and the expression of CD80 and CD86 on AMs were also investigated. IL-4 and IL-5 levels were significantly higher in the co-cultures from patients with IPF than in those from normal volunteers. IL-2, interferon-gamma (IFN-gamma), and IL-10 production in these co-cultures did not differ. IL-10 suppressed T-cell proliferation in co-cultures with AMs from healthy volunteers (smokers and nonsmokers), but not with AMs from patients with IPF. Expression of CD80 and CD86 on AMs from these groups did not differ. Thus, the altered accessory cell function of alveolar macrophages from patients with idiopathic pulmonary fibrosis may possibly relate to the pattern of type-2 T-helper cytokine production in response to inflammation.

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