Enhancement of Cytotoxicity of Active Macrophages by Mycoplasma: Role of Mycoplasma‐Associated Induction of Tumor Necrosis Factor‐α (TNF‐α) in Macrophages

Tumor necrosis factor-alpha (TNF-alpha)-inducing activity of several mycoplasmas including Mycoplasma pneumoniae, a causative agent in human respiratory infectious diseases, was investigated. Purified peritoneal macrophages from BALB/c mice markedly enhanced their cytotoxic activity to Meth A cells, when cultured with either viable or non-viable mycoplasmas. The supernatants of the macrophage culture with mycoplasmas, M. pneumoniae and Acholeplasma laidlawii, showed the potent cytotoxic activity to TNF-alpha-sensitive L cells but not to TNF-alpha-insensitive L cells. Addition of anti-TNF-alpha antiserum inhibited completely the cytotoxic activity of these supernatants, indicating that a major part of the cytotoxic activity might be due to TNF-alpha. Various other mycoplasmas, either glucose- or arginine-utilizing species, as far as tested showed also the potent activity to produce TNF-alpha. These results strongly suggest the possibility that mycoplasmas possess the activity of TNF-alpha induction which might be responsible for a part of enhancement of cytotoxic activity of macrophages and resistance to infection with mycoplasmas in vivo.