Interferon-γ production is suppressed in thermally injured mice: Decreased production of regulatory cytokines and corresponding receptors

Tracy Toliver-Kinsky, Tushar K. Varma, Cheng Y. Lin, David Herndon, Edward R. Sherwood

Research output: Contribution to journalArticle

42 Citations (Scopus)

Abstract

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-γ 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-γ induction in the major IFN-γ-producing cell types of the spleen. Additionally, effects on key IFN-γ-regulatory cytokines were examined after bacterial challenge. We report that in vivo induction of IFN-γ in natural killer lymphocytes is suppressed in burned mice. Splenic IFN-γ 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-γ-inducing factors. IFN-γ production could be restored by neutralization of the upregulated cytokine IL-10. Induction of the IFN-γ-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-γ 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-γ is due to deficient production of inducing factors and their receptors, leading to severe impairments in cellular IFN-γ induction pathways.

Original languageEnglish (US)
Pages (from-to)322-330
Number of pages9
JournalShock
Volume18
Issue number4
StatePublished - Oct 2002

Fingerprint

Cytokine Receptors
Interferons
Cytokines
Interleukin-12
Burns
Wounds and Injuries
Lymphocytes
Interleukin-10
Interleukin-2
Interleukin-15 Receptors
Hot Temperature
Interleukin-15
Interleukin-18
Body Surface Area
Opportunistic Infections
Immunosuppression
Dendritic Cells
Sepsis
Anti-Inflammatory Agents
Spleen

Keywords

  • Burn
  • Infection
  • Inflammation
  • Interleukin 12
  • Interleukin 15
  • Interleukin 18
  • Lymphocyte
  • Macrophage

ASJC Scopus subject areas

  • Physiology
  • Critical Care and Intensive Care Medicine

Cite this

Interferon-γ production is suppressed in thermally injured mice : Decreased production of regulatory cytokines and corresponding receptors. / Toliver-Kinsky, Tracy; Varma, Tushar K.; Lin, Cheng Y.; Herndon, David; Sherwood, Edward R.

In: Shock, Vol. 18, No. 4, 10.2002, p. 322-330.

Research output: Contribution to journalArticle

Toliver-Kinsky, Tracy ; Varma, Tushar K. ; Lin, Cheng Y. ; Herndon, David ; Sherwood, Edward R. / Interferon-γ production is suppressed in thermally injured mice : Decreased production of regulatory cytokines and corresponding receptors. In: Shock. 2002 ; Vol. 18, No. 4. pp. 322-330.
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