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A novel IL-18BP ELISA shows elevated serum IL-18BP in sepsis and extensive decrease of free IL-18.
Novick, D; Schwartsburd, B; Pinkus, R; Suissa, D; Belzer, I; Sthoeger, Z; Keane, W F; Chvatchko, Y; Kim, S H; Fantuzzi, G; Dinarello, C A; Rubinstein, M.
Afiliación
  • Novick D; Department of Molecular Genetics, The Weizmann Institute of Science, Rehovot, 76100, Israel.
Cytokine ; 14(6): 334-42, 2001 Jun 21.
Article en En | MEDLINE | ID: mdl-11497494
IL-18 binding protein (IL-18BP) is a circulating antagonist of the proinflammatory Th1 cytokine IL-18. It effectively blocks IL-18 by forming a 1:1 high affinity (Kd=400 pM) complex, exhibiting a very low dissociation rate. We have developed a sandwich ELISA for IL-18BPa and determined its limit of detection (62 pg/ml). Interference by IL-18 and related cytokines, as well as cross reactivity with other IL-18BP isoforms (b, c, and d) were determined. Using this ELISA, we measured serum IL-18BPa in large cohorts of healthy individuals and in septic patients. Serum IL-18BPa in healthy individuals was 2.15+/-0.15 ng/ml (range 0.5-7 ng/ml). In sepsis, the level rose to 21.9+/-1.44 ng/ml (range 4-132 ng/ml). Total IL-18 was measured in the same sera by an electrochemiluminescence assay and free IL-18 was calculated based on the mass action law. Total IL-18 was low in healthy individuals (64+/-17 pg/ml) and most of it ( approximately 85%) was in its free form. Total IL-18 and IL-18BPa were both elevated in sepsis patients upon admission (1.5+/-0.4 ng/ml and 28.6+/-4.5 ng/ml, respectively). At these levels, most of the IL-18 is bound to IL-18BPa, however the remaining free IL-18 is still higher than in healthy individuals. We conclude that IL-18BPa considerably inhibits circulating IL-18 in sepsis. Yet, exogenous administration of IL-18BPa may further reduce circulating IL-18 activity.
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Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Ensayo de Inmunoadsorción Enzimática / Glicoproteínas / Sepsis / Interleucina-18 Límite: Animals / Humans Idioma: En Revista: Cytokine Asunto de la revista: ALERGIA E IMUNOLOGIA Año: 2001 Tipo del documento: Article País de afiliación: Israel Pais de publicación: Reino Unido
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Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Ensayo de Inmunoadsorción Enzimática / Glicoproteínas / Sepsis / Interleucina-18 Límite: Animals / Humans Idioma: En Revista: Cytokine Asunto de la revista: ALERGIA E IMUNOLOGIA Año: 2001 Tipo del documento: Article País de afiliación: Israel Pais de publicación: Reino Unido