MDHM, a macrophage-stimulatory product of Mycoplasma fermentans, leads to in vitro interleukin-1 (IL-1), IL-6, tumor necrosis factor, and prostaglandin production and is pyrogenic in rabbits

Abstract

Mycoplasmafermentans-derived high-molecular-weight material (MDHM) was originally discovered because of its capacity to generate, through the induction of monokine synthesis, cytolytic T lymphocytes in concanavalin A-stimulated thymocyte cultures. This study shows that MDHM-activated macrophages not only released interleukin-6 (IL-6) but also exhibited increased synthesis of cell-associated IL-1 as well as liberation of tumor necrosis factor and prostaglandin. We determined 6-keto prostaglandin Fla since it is the stable metabolite of the bioactive prostacyclin. MDHM appeared to be as potent as lipopolysaccharide in inducing the synthesis of these mediators. Priming with gamma interferon further increased MDHM-mediated IL-6 release. Since monokines can be pyrogenic, we tested the effects of an intravenous injection of MDHM on rectal temperatures and leukocyte counts in rabbits. At 1 h after a bolus injection of MDHM, leukocyte counts dropped to about 35% of the initial values, reflecting a decrease in both lymphocytes and granulocytes. At 4 to 6 h after injection, granulocyte counts began to increase again, whereas lymphocyte counts remained low. No leukocytosis was noted during this time. The lack of leukocytosis can be explained by the failure of MDHM-stimulated macrophages to release IL-1. The property of MDHM to cause IL-6 release from macrophages and the IL-6 growth dependency of the 7TD1 hybridoma cell line were made use of in a coculture assay system to quantitate the activity of MDHM. With this method and macrophages from C3HtHeJ lipopolysaccharide-nonresponder mice, MDHM activity was found to be equally distributed in the mycoplasma growth medium and the sedimented mycoplasmas after sonication.

MDHM, a macrophage-activating product of Mycoplasma fermentans, stimulates murine macrophages to synthesize nitric oxide and become tumoricidal

“…Miihlradt, unpublished). As previously reported [3], MDHM is membrane-associated. It is no common lipid, as delipidation did not remove NO releasing activity from the residue.…”

“…The lag 228 phase can possibly be attributed to the time required for the action of IFN-y, since Stuehr and Marietta have shown that macrophages, primed in vivo by a BCG infection, can shortly after obtaining a second signal by, in their case LPS, begin to release nitrite [14]. Another explanation for the lag phase is a requirement for upregulation of NO synthase by TNF [24], which we have shown to be maximally released by MDHMactivated macrophages after a delay of 6 h [3]. The data in Fig.…”

“…In vitro effects of mycoplasmas or their products on immune cells range from mitogenic activity on B [1] or T [2] cells to activation of macrophages, resulting in release of cytokines [3][4][5][6], of induction of class II MHC molecules [7] or of the cytocidal state [8,9]. With the exception of the well characterized Mycoplasma arthritidisderived MAS, which is a small protein [2] with superantigen properties [10], such effects are often difficult to interpret or compare since more than one active molecular entity could be present in the often crude mycoplasmal preparations (see e.g.…”

“…[5]), and the particular effect under study could be an indirect one. Thus, a macrophage stimulatory activity from Mycoplasma fermentans, named MDHM (mycoplasma-derived high molecular weight material), was originally detected through its indirect effects on T cell differentiation [4,11], although the primary effects of MDHM are activation of macrophages to production of IL-1, IL-6, TNF and arachidonate metabolites [3].…”

Elevated concentrations of interleukin‐6 in intra‐amniotic infection with Ureaplasma urealyticum in asymptomatic women during

“…Bacterial infection is one of several factors that cause increased levels of IL-6 (11). Mycoplasmas, the most prevalent bacteria isolated from AFs, were previously shown to induce production of IL-6 both in vitro and in vivo (12,13). We found high levels of IL-6 in the AFs that were infected with U.urealyticum.…”