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Release of tumor necrosis factor alpha by human peritoneal macrophages in response to toxic shock syndrome toxin-1
R P Buyalos1, E M Rutanen, E Tsui
1Department of Obstetrics and Gynecology, University of California, Los Angeles.
Abstract:
We examined the release in vitro of tumor necrosis factor-alpha (TNF-alpha) by peritoneal macrophages and peripheral blood monocytes following incubation with toxic shock syndrome toxin-1 (TSST-1). We obtained peritoneal macrophages from 22 women at laparoscopy and peripheral blood monocytes from four healthy women during both the midfollicular and midluteal phases of the menstrual cycle. The samples were incubated for 24 hours at 37 C with 10(-2)-10(4) ng/mL of TSST-1 or 10(4) ng/mL of bacterial endotoxin. Tumor necrosis factor-alpha activity was determined with a bioassay using an actinomycin D-sensitized WEHI-164 murine fibrosarcoma cell line. Twenty-four-hour incubation with TSST-1 resulted in a dose-dependent release of TNF-alpha by both peritoneal macrophages (maximal response 554 +/- 97 U of activity) and peripheral blood monocytes (maximal response 478 +/- 81 U of activity). We observed enhanced TNF-alpha release by peritoneal macrophages from women with endometriosis, compared with those without endometriosis, at a concentration of 10(4) ng/mL of TSST-1 (704 +/- 134 versus 354 +/- 103 U of activity; P less than .05). These data support the theory that the metabolic and physiologic derangements of perimenstrual toxic shock syndrome may be partially mediated by TNF-alpha released by peritoneal macrophages as a result of exposure to TSST-1.
Insights
Toxic shock syndrome toxin-1 (TSST-1) triggers tumor necrosis factor-alpha (TNF-alpha) release from immune cells. This inflammatory mediator may contribute to toxic shock syndrome symptoms, particularly in women with endometriosis.
Area of Science:
- Immunology
- Toxicology
- Gynecology
Background:
- Toxic shock syndrome (TSS) is a severe illness caused by bacterial toxins.
- Tumor necrosis factor-alpha (TNF-alpha) is a key inflammatory cytokine implicated in various disease states.
- The role of TSST-1 in TNF-alpha production by human immune cells requires further elucidation.
Purpose of the Study:
- To investigate the in vitro release of TNF-alpha by human peritoneal macrophages and peripheral blood monocytes stimulated with TSST-1.
- To compare TNF-alpha release in women with and without endometriosis.
- To explore the potential role of TNF-alpha in the pathophysiology of TSS.
Main Methods:
- Peritoneal macrophages were obtained from women undergoing laparoscopy, and peripheral blood monocytes were isolated from healthy women.
- Cell samples were incubated with varying concentrations of TSST-1 or bacterial endotoxin.
- TNF-alpha activity was quantified using a bioassay with a sensitive murine fibrosarcoma cell line.
Main Results:
- TSST-1 induced a dose-dependent release of TNF-alpha from both peritoneal macrophages and peripheral blood monocytes.
- Peritoneal macrophages from women with endometriosis exhibited significantly higher TNF-alpha release upon TSST-1 stimulation compared to those without endometriosis.
- Bacterial endotoxin also stimulated TNF-alpha release, serving as a positive control.
Conclusions:
- TSST-1 is a potent stimulator of TNF-alpha release from human macrophages and monocytes.
- Elevated TNF-alpha production in response to TSST-1 by peritoneal macrophages may contribute to the pathogenesis of TSS, especially in women with endometriosis.
- These findings support the hypothesis that TNF-alpha plays a partial role in the metabolic and physiological disturbances associated with TSS.