title: Inflammatory protein profile during systemic high dose interleukin-2 administration.
abstract: Systemic interleukin-2 (IL-2) administration induces an assortment of downstream effects whose biological and therapeutic significance remains unexplored mostly because of the methodological inability to globally address their complexity. Protein array analysis of sera from patients with renal cell carcinoma obtained prior and during high-dose IL-2 therapy had previously revealed extensive alterations in expression of the soluble factors analyzed, whose discovery was limited by the number of capture antibodies selected for protein detection. Here, we expanded the analysis to SELDI-TOF-MS and quantitative protein analysis (nephelometry). All cytokines/chemokines detected by protein arrays were below the SELDI detection limit, while novel IL-2-specific changes in expression of acute-phase reactants and high-density lipoprotein metabolites could be identified. Serum amyloid protein A (SAA) and C-reactive protein expression were consistently up-regulated after four doses of IL-2, while other proteins were down-regulated. These findings were confirmed by SELDI immunoaffinity capture and nephelometry. Immunoaffinity capture revealed different, otherwise undetectable, isoforms of SAA. A linear correlation between peak area by SELDI and protein concentration by nephelometry was observed. Overall distinct yet complementary information was obtained using different platforms, which may better illustrate complex phenomena such as the systemic response to biological response modifiers.
authors.affiliation: Department of Human Morphology and Applied Biology, University of Pisa, Pisa, Italy.
authors.forename: Leonardo
authors.initials: L
authors.lastname: Rossi
authors.forename: Brian M
authors.initials: BM
authors.lastname: Martin
authors.forename: Glen L
authors.initials: GL
authors.lastname: Hortin
authors.forename: Richard L
authors.initials: RL
authors.lastname: White
authors.forename: Mareva
authors.initials: M
authors.lastname: Foster
authors.forename: Ramy
authors.initials: R
authors.lastname: Moharram
authors.forename: David
authors.initials: D
authors.lastname: Stroncek
authors.forename: Ena
authors.initials: E
authors.lastname: Wang
authors.forename: Francesco M
authors.initials: FM
authors.lastname: Marincola
authors.forename: Monica C
authors.initials: MC
authors.lastname: Panelli
mesh_terms: D015415:Biomarkers / Q000097:blood*; D002292:Carcinoma, Renal Cell / Q000188:drug therapy / Q000378:metabolism; D015180:Electrophoresis, Gel, Two-Dimensional; D006801:Humans; D007376:Interleukin-2 / Q000008:administration & dosage*; D007680:Kidney Neoplasms / Q000188:drug therapy / Q000378:metabolism; D040081:Protein Array Analysis; D019032:Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization
chemical_list: D015415:Biomarkers; D007376:Interleukin-2