Insulin-like growth factor-I/insulin-like growth factor binding protein-3 alters lymphocyte responsiveness following severe burn

Steven Wolf, Kenneth J. Woodside, Roque J. Ramirez, Makiko Kobayashi, Fujio Suzuki, David Herndon

Research output: Contribution to journalArticle

16 Citations (Scopus)

Abstract

Purpose Following severe burn, patients are immunocompromised, making them at increased risk for infection. Exogenous growth hormone has been shown to partially restore immune function. Herein, we investigated Th1/Th2 cytokine profiles and cellular proliferation in isolated mononuclear cells after treatment with exogenous insulin-like growth factor-I (IGF-I), the indirect mediator of many growth hormone effects, in severely burned patients. Methods Eight children and 2 adults with >20% total body surface area burns were prospectively randomized to receive either placebo or 4 mg/kg rhIGF-I/IGFBP-3 for one-week intervals (2 groups), with another group receiving placebo for both cycles. Normal children were examined for comparison. Isolated whole blood lymphocyte production of Th1 (IL-2, IFN-γ) and Th2 (IL-4, IL-10) cytokines, and proliferative responses to specific T-cell mitogens were measured. Results Depressed Th1 and exaggerated Th2 cytokine responses were seen in all burned subjects compared to non-burned controls (P < 0.05). IL-2 and IFN-γ production increased in patients treated with IGF-I/IGFBP-3 (P < 0.05). IL-4 production significantly decreased, while IL-10 levels did not change. Cytokine production did not change in those receiving two courses of placebo. Proliferative responses of isolated mononuclear cells to IL-2 as a Th1 specific mitogen increased with IGF-I/IGFBP-3 treatment (P < 0.05). Conclusions Following severe burn, a shift occurs toward a predominant Th2 phenotype. Exogenous IGF-I/IGFBP-3 treatment partially reverses this response.

Original languageEnglish (US)
Pages (from-to)255-261
Number of pages7
JournalJournal of Surgical Research
Volume117
Issue number2
DOIs
StatePublished - Apr 2004

Fingerprint

Insulin-Like Growth Factor Binding Protein 3
Insulin-Like Growth Factor I
Lymphocytes
Cytokines
Interleukin-2
Placebos
Mitogens
Interleukin-4
Interleukin-10
Growth Hormone
Body Surface Area
Immunocompromised Host
Burns
Therapeutics
Cell Proliferation
T-Lymphocytes
Phenotype
Infection

Keywords

  • Burns
  • IFN-γ
  • IGF-I
  • IGFBP-3
  • IL-10
  • IL-2
  • IL-4
  • Immunomodulation
  • Lymphocytes
  • Th1/Th2 profile

ASJC Scopus subject areas

  • Surgery

Cite this

Insulin-like growth factor-I/insulin-like growth factor binding protein-3 alters lymphocyte responsiveness following severe burn. / Wolf, Steven; Woodside, Kenneth J.; Ramirez, Roque J.; Kobayashi, Makiko; Suzuki, Fujio; Herndon, David.

In: Journal of Surgical Research, Vol. 117, No. 2, 04.2004, p. 255-261.

Research output: Contribution to journalArticle

Wolf, Steven ; Woodside, Kenneth J. ; Ramirez, Roque J. ; Kobayashi, Makiko ; Suzuki, Fujio ; Herndon, David. / Insulin-like growth factor-I/insulin-like growth factor binding protein-3 alters lymphocyte responsiveness following severe burn. In: Journal of Surgical Research. 2004 ; Vol. 117, No. 2. pp. 255-261.
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AU - Herndon, David

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AB - Purpose Following severe burn, patients are immunocompromised, making them at increased risk for infection. Exogenous growth hormone has been shown to partially restore immune function. Herein, we investigated Th1/Th2 cytokine profiles and cellular proliferation in isolated mononuclear cells after treatment with exogenous insulin-like growth factor-I (IGF-I), the indirect mediator of many growth hormone effects, in severely burned patients. Methods Eight children and 2 adults with >20% total body surface area burns were prospectively randomized to receive either placebo or 4 mg/kg rhIGF-I/IGFBP-3 for one-week intervals (2 groups), with another group receiving placebo for both cycles. Normal children were examined for comparison. Isolated whole blood lymphocyte production of Th1 (IL-2, IFN-γ) and Th2 (IL-4, IL-10) cytokines, and proliferative responses to specific T-cell mitogens were measured. Results Depressed Th1 and exaggerated Th2 cytokine responses were seen in all burned subjects compared to non-burned controls (P < 0.05). IL-2 and IFN-γ production increased in patients treated with IGF-I/IGFBP-3 (P < 0.05). IL-4 production significantly decreased, while IL-10 levels did not change. Cytokine production did not change in those receiving two courses of placebo. Proliferative responses of isolated mononuclear cells to IL-2 as a Th1 specific mitogen increased with IGF-I/IGFBP-3 treatment (P < 0.05). Conclusions Following severe burn, a shift occurs toward a predominant Th2 phenotype. Exogenous IGF-I/IGFBP-3 treatment partially reverses this response.

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