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Inflammatory protein profile during systemic high dose interleukin‐2 administration
Author(s) -
Rossi Leonardo,
Martin Brian M.,
Hortin Glen L.,
White Richard L.,
Foster Mareva,
Moharram Ramy,
Stroncek David,
Wang Ena,
Marincola Francesco M.,
Panelli Monica C.
Publication year - 2006
Publication title -
proteomics
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.26
H-Index - 167
eISSN - 1615-9861
pISSN - 1615-9853
DOI - 10.1002/pmic.200500004
Subject(s) - nephelometry , acute phase protein , serum amyloid a , interleukin 6 , protein array analysis , systemic administration , chemokine , antibody , chemistry , microbiology and biotechnology , biology , immunology , inflammation , gene expression , biochemistry , dna microarray , gene , in vivo
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.