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Interleukin-1 receptor antagonist decreases cerebrospinal fluid nitric oxide levels and increases vasopressin secretion in the late phase of sepsis in rats

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Abstract

The aim of this study was to analyze the effect of IL-1ra (an Interleukin-1 receptor antagonist) on sepsis-induced alterations in vasopressin (AVP) and nitric oxide (NO) levels. In addition, IL-1ra effect on the hypothalamic nitric oxide synthase (NOS) activities and survival rate was also analyzed. After Wistar rats were intracerebroventricular injected with IL-1ra (9 pmol) or vehicle (PBS 0.01 M), sepsis was induced by cecal-ligation and puncture (CLP). Blood, CSF, and hypothalamic samples were collected from different groups of rats (n = 8/group) after 4, 6, and 24 h. AVP and NO levels were greatly increased in CLP. Both total NOS and inducible NOS (iNOS) activities were also greatly increased in CLP rats. These changes in AVP, NO, and NOS were not observed in sham-operated control rats. IL-1ra administration did not alter plasma AVP levels after 4 and 6 h as compared to vehicle in CLP animals but after 24 h were significantly (P < 0.01) higher in IL-1ra-treated animals. IL-1ra administration significantly (P < 0.01) decreased NO concentration in CSF but not in plasma. Both total NOS and iNOS activities were also significantly decreased by IL-1ra at 24 h in CLP animals. Moreover, the 24 h survival rate of IL-1ra-treated rats increased by 38 % in comparison to vehicle administered animals. The central administration of IL-1ra increased AVP secretion in the late phase of sepsis which was beneficial for survival. We believe that one of the mechanisms for this effect of IL-1ra is through reduction of NO concentration in CSF and hence lower hypothalamic iNOS activities in the septic rats.

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Acknowledgments

The authors thank Nadir Martins Fernandes and Milene Mantovani for the technical assistant. Fernando Queiróz Cunha and José Antunes Rodrigues provided the infrastructure for the NOS activity analysis. Financial support from Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP) is gratefully acknowledged.

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The authors have nothing to disclose.

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Authors and Affiliations

  1. Department of Morphology, Physiology and Basic Pathology, School of Dentistry of Ribeirão Preto, Avenida do Café s/n CEP, Ribeirão Preto, SP, 14040-904, Brazil

    Fazal Wahab, Lucas F. Tazinafo, Fábio A. Aguila & Maria José A. Rocha

  2. Department of Specialized Nursing, Nursing School of Ribeirão Preto, University of São Paulo, Ribeirão Preto, SP, Brazil

    Evelin C. Cárnio & Marcelo E. Batalhão

Authors
  1. Fazal Wahab
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  2. Lucas F. Tazinafo
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  4. Fábio A. Aguila
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  6. Maria José A. Rocha
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Correspondence to Maria José A. Rocha.

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Wahab, F., Tazinafo, L.F., Cárnio, E.C. et al. Interleukin-1 receptor antagonist decreases cerebrospinal fluid nitric oxide levels and increases vasopressin secretion in the late phase of sepsis in rats. Endocrine 49, 215–221 (2015). https://doi.org/10.1007/s12020-014-0452-2

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  • DOI: https://doi.org/10.1007/s12020-014-0452-2

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