Elimination half-lives of interleukin-6 and cytokine-induced neutrophil chemoattractant-1 synthesized in response to inflammatory stimulation in rats

The elimination half-lives of in Interleukin-6 (IL-6) and cytokine-induced neutrophil chemoattractant-1 (CINC-1) in rats after inflammatory stimulation were investigated. Five male Sprague-Dawley rats were used (age, 9 weeks; body weight, 235–375 g). Turpentine oil was intramuscularly injected at a dose of 2 mL/kg body weight to induce acute inflammation. Blood was collected pre-injection and 6, 12, 24, 36, 48, 60, 72, 84, and 96 h after the turpentine oil injection. Serum concentrations of IL-6, CINC-1, and α2-macroglobulin (α2M) were measured by enzyme-linked immunosorbent assay. Half-lives were calculated as 0.693/elimination rate constant. The serum concentration of α2M peaked at 48 h after turpentine oil injection. Serum concentrations of IL-6 and CINC-1 increased and peaked at 12 and 24 h, respectively. The terminal elimination half-lives of IL-6 and CINC-1 were 15.5 and 29.9 h, respectively. The half-life of CINC-1 was significantly longer than that of IL-6 (P=0.006). These results suggested that these cytokines synthesized in response to inflammatory stimulation were rapidly eliminated in rats. The serum concentrations of these cytokines should be measured at an early stage if these cytokines will be used as surrogate inflammatory markers instead of acute-phase proteins.

[1]  H. Wada,et al.  Phase I study of pegylated interferon‐alpha‐2b as an adjuvant therapy in Japanese patients with malignant melanoma , 2016, The Journal of dermatology.

[2]  I. Nestorov,et al.  COMPARE: Pharmacokinetic profiles of subcutaneous peginterferon beta‐1a and subcutaneous interferon beta‐1a over 2 weeks in healthy subjects , 2016, British journal of clinical pharmacology.

[3]  R. Bermel,et al.  Incidence, characterization, and clinical impact analysis of peginterferon beta1a immunogenicity in patients with multiple sclerosis in the ADVANCE trial , 2016, Therapeutic advances in neurological disorders.

[4]  R. Hamatake,et al.  Pharmacokinetic Characteristics, Pharmacodynamic Effect and In Vivo Antiviral Efficacy of Liver-Targeted Interferon Alpha , 2015, PloS one.

[5]  E. Momotani,et al.  Elimination Half-Lives of Acute Phase Proteins in Rats and Beagle Dogs During Acute Inflammation , 2015, Inflammation.

[6]  C. Vivek,et al.  Turpentine oil induced inflammation decreases absorption and increases distribution of phenacetin without altering its elimination process in rats , 2013, European Journal of Drug Metabolism and Pharmacokinetics.

[7]  F. Beaudry,et al.  Pharmacokinetics of ketamine and xylazine in young and old Sprague-Dawley rats. , 2013, Journal of the American Association for Laboratory Animal Science : JAALAS.

[8]  T. Kuribayashi,et al.  Comparison of α2-Macroglobulin Synthesis by Juvenile vs. Mature Rats after Identical Inflammatory Stimulation , 2013, Inflammation.

[9]  E. Momotani,et al.  Impairment of α(2)-macroglobulin synthesis in experimental hepatopathic rats treated with turpentine oil. , 2012, Experimental animals.

[10]  G. Foster.  Pegylated Interferons for the Treatment of Chronic Hepatitis C , 2012, Drugs.

[11]  T. Kuribayashi,et al.  Relationship between production of acute-phase proteins and strength of inflammatory stimulation in rats , 2011, Laboratory animals.

[12]  M. Matsumoto,et al.  Kinetics of α 2-macroglobulin and α 1-acid glycoprotein in rats subjected to repeated acute inflammatory stimulation , 2010, Laboratory animals.

[13]  T. Kuribayashi,et al.  The effects of interleukin-6 and cytokine-induced neutrophil chemoattractant-1 on α₂-macroglobulin production in rats. , 2010, Experimental animals.

[14]  D. Cutler,et al.  Pegylating IFNs at His-34 Improves the in Vitro Antiviral Activity Through the JAK/STAT Pathway , 2004, Antiviral chemistry & chemotherapy.

[15]  S. Yamamoto,et al.  Serum α2-macroglobulin and cytokine measurements in an acute inflammation model in rats , 2002, Laboratory animals.

[16]  Shizuo Yamamoto,et al.  Determination of α2-macroglobulin concentrations in healthy rats of various ages and rats inoculated with turpentine oil by an enzyme-linked immunosorbent assay , 2002 .

[17]  T. Whiteside.  Cytokine assays. , 2002, BioTechniques.

[18]  S. Yamamoto,et al.  Variation of serum alpha2-macroglobulin concentration in healthy rats and rats inoculated with Staphylococcus aureus or subjected to surgery. , 2001, Comparative medicine.

[19]  V. Iacono,et al.  The cytokines: a review of interleukins. , 1997, Periodontal clinical investigations : official publication of the Northeastern Society of Periodontists.

[20]  G. Morgan.  Lecture Notes on Immunology , 1988 .