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Role of interleukin-10 in monocyte hyporesponsiveness associated with septic shock
1Saint Vincents Hospital and Medical Center, New York Medical College, NY, USA.
Objectives:
The purpose of this study was to examine the pattern of tumor necrosis factor (TNF)-alpha and interleukin (IL)-10 release in endotoxin-stimulated septic monocytes and to determine the role of IL-10 and transforming growth factor (TGF)-beta in monocyte hyporesponsiveness during septic shock.
Design:
Monocytes isolated from ten healthy controls and ten patients with septic shock were incubated with endotoxin and cytokine release was assessed. Next, normal monocytes were incubated with either normal or septic serum and stimulated with endotoxin. Finally, normal monocytes were incubated with septic serum either with anti-IL-10 antibodies or anti-TGF-beta antibodies and then stimulated with endotoxin.
Measurements:
TNF-alpha, IL-10, and TGF-beta levels were measured in the serum and in culture supernatants by enzyme-linked immunosorbent assay.
Setting:
Research laboratory.
Main Results:
IL-10 and TNF-alpha levels were significantly increased in septic serum, whereas TGF-beta levels were not different from controls. Normal monocytes increased TNF-alpha and IL-10 release in response to endotoxin. In contrast, septic monocyte TNF-alpha release was attenuated in response to endotoxin (1.8 +/- 0.5 vs. 1.0 +/- 0.4 ng/mL, stimulated vs. baseline), whereas IL-10 release increased significantly from baseline (173 +/- 91 vs. 8 +/- 4 pg/mL, stimulated vs. baseline). Incubation of normal monocytes with septic serum attenuated TNF-alpha release in response to endotoxin (32% +/- 8% of normal serum; p < .01), whereas IL-10 release was increased (285% +/- 84% of normal serum; p < .05). When normal monocytes were incubated with septic serum combined with anti-IL-10 antibodies, TNF-alpha release increased significantly to 75% +/- 17% of normal serum (p < .05 vs. septic serum alone). Incubation of normal monocytes with anti-TGF-beta antibodies did not significantly affect either TNF-alpha or IL-10 release in response to endotoxin.
Conclusion:
Monocytes from patients with septic shock exhibit persistent IL-10 release at a time when TNF-alpha release is downregulated. The continued release of IL-10 may contribute to impairment of monocyte proinflammatory cytokine release and the development of immune dysfunction in septic shock.