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Inflammatory protein profile during systemic high dose interleukin-2 administration

Leonardo Rossi1, Brian M Martin, Glen L Hortin

  • 1Department of Human Morphology and Applied Biology, University of Pisa, Pisa, Italy.

Proteomics
|December 13, 2005
PubMed

Insights

Systemic interleukin-2 (IL-2) therapy alters protein expression in renal cell carcinoma patients. Novel changes in acute-phase reactants and HDL metabolites were identified using advanced proteomic techniques.

Area of Science:

  • Biochemistry
  • Immunology
  • Proteomics

Background:

  • Systemic interleukin-2 (IL-2) administration causes complex downstream effects.
  • Previous protein array analysis revealed alterations in soluble factors during IL-2 therapy for renal cell carcinoma (RCC).
  • Methodological limitations hindered a comprehensive understanding of these systemic effects.

Purpose of the Study:

  • To expand proteomic analysis of serum from RCC patients undergoing IL-2 therapy.
  • To identify novel IL-2-specific protein expression changes beyond cytokine/chemokine profiles.
  • To compare SELDI-TOF-MS and nephelometry for analyzing systemic responses to biological response modifiers.

Main Methods:

  • Serum samples from RCC patients before and during high-dose IL-2 therapy were analyzed.
  • Expanded analysis included Surface-Enhanced Laser Desorption/Ionization Time-of-Flight Mass Spectrometry (SELDI-TOF-MS) and nephelometry.
  • SELDI immunoaffinity capture and quantitative protein analysis were employed.

Main Results:

  • Cytokines/chemokines detected by protein arrays were below SELDI detection limits.
  • Significant IL-2-specific changes identified in acute-phase reactants and high-density lipoprotein (HDL) metabolites.
  • Serum amyloid protein A (SAA) and C-reactive protein were consistently upregulated post-IL-2; other proteins downregulated.
  • SELDI immunoaffinity capture revealed previously undetectable SAA isoforms.
  • A linear correlation was observed between SELDI peak area and nephelometry protein concentration.

Conclusions:

  • Combined proteomic platforms provide distinct yet complementary insights into systemic IL-2 response.
  • Novel biomarkers, including SAA and CRP, are modulated by IL-2 therapy in RCC.
  • Advanced proteomic techniques are crucial for dissecting the complexity of biological response modifier effects.

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