Interferon-gamma production is suppressed in thermally injured mice: decreased production of regulatory cytokines and corresponding receptors.

Toliver-Kinsky TE, Varma TK, Lin CY, Herndon DN, Sherwood ER
Shock. 2002 18 (4): 322-30

PMID: 12392275 · DOI:10.1097/00024382-200210000-00006

Thermal injury to 40% or more of the total body surface area poses a significant risk for the development of opportunistic infections that increase complications and mortality. Altered cytokine induction profiles, including suppression of the Th1 cytokines IFN-gamma and IL-12 and elevations in the anti-inflammatory cytokine IL-10, are believed to contribute to burn-associated immunosuppression and the development of sepsis. The specific changes that lead to altered cytokine production following major burns are not known. We examined the effects of burn injuries to 40% of the mouse body surface on IFN-gamma induction in the major IFN-gamma-producing cell types of the spleen. Additionally, effects on key IFN-gamma-regulatory cytokines were examined after bacterial challenge. We report that in vivo induction of IFN-gamma in natural killer lymphocytes is suppressed in burned mice. Splenic IFN-gamma was suppressed at both the mRNA and protein levels. Early suppression was associated with impairments in both the macrophage/dendritic cell and lymphocyte populations, whereas persistent suppression was associated with impaired lymphocyte function and decreased responsiveness to IFN-gamma-inducing factors. IFN-gamma production could be restored by neutralization of the upregulated cytokine IL-10. Induction of the IFN-gamma-inducers IL-15, IL-12, and IL-2 was also impaired after burn injury, whereas IL-18 levels remained unaffected. Exogenous application of these suppressed cytokines to isolated splenocytes did not restore IFN-gamma to sham levels, indicating a loss of responsiveness to these factors. Expression of the IL-2, IL-12, and IL-15 receptors was suppressed after thermal injury. We conclude that burn-associated suppression of IFN-gamma is due to deficient production of inducing factors and their receptors, leading to severe impairments in cellular IFN-gamma induction pathways.

MeSH Terms (17)

Animals Burns Cells, Cultured Coculture Techniques Cytokines Female Interferon-gamma Interleukin-10 Interleukin-12 Killer Cells, Natural Lymphocytes Macrophages Mice Mice, Inbred BALB C Pseudomonas aeruginosa Receptors, Cytokine Spleen

Connections (1)

This publication is referenced by other Labnodes entities: