The role of nitric oxide in the effects of the pro-inflammatory cytokine IL-1β on the hypercapnic ventilation response

Authors

DOI:

https://doi.org/10.33910/2687-1270-2020-1-2-101-107

Keywords:

cytokines, interleukin-1, hypercapnia, respiratory chemoreflex, breathing, ventilation, NO-synthase

Abstract

The aim of the current study was to compare the respiratory effects of IL-1β before and after pre-treatment with L-NAME, a nonspecific NO-synthases inhibitor.

The experiments were performed on tracheotomised anaesthetised rats. The hypercapnic ventilatory response was measured by means of the rebreathing method using a hyperoxic-hypercapnic gas mixture (60 % O2, 7 % CO2) before and after the cerebroventricular administration of human recombinant IL-1β in the amount of 500 ng dissolved in 10 μl of saline. In order to determine the role of the NO-pathway in the ventilatory effects of IL-1β, L-NAME, a non-specific inhibitor of NO-synthase, was used.

As a result, the slope of the ventilatory response to carbon dioxide decreased almost twofold at 40 min. after the cerebroventricular administration of IL-1β. In contrast, the basal level of lung ventilation increased after the elevation of IL-1β in CSF. L-NAME pre-treatment reduced these respiratory effects of IL-1β. The data indicate that the inhibitor of NO-synthase significantly reduces the effect of the pro-inflammatory cytokine IL-1β.

The authors conclude that the ability of IL-1β to enhance basal ventilation and to reduce the ventilatory hypercapnic response may be mediated by NO-dependent mechanisms.

References

ЛИТЕРАТУРА

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REFERENCES

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Aleksandrova, N. P., Danilova, G. A., Aleksandrov, V. G. (2015) Cyclooxygenase pathway in modulation of the ventilatory response to hypercapnia by interleukin-1β in rats. Respiratory Physiology & Neurobiology, vol. 209, pp. 85–90. PMID: 25511383. DOI: 10.1016/j.resp.2014.12.006 (In English)

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Churchill, L., Taishi, P., Wang, M. et al. (2006) Brain distribution of cytokine mRNA induced by systemic administration of interleukin-1β or tumor necrosis factor α. Brain Research, vol. 1120, no. 1, pp. 64–73. PMID: 17022949. DOI: 10.1016/j.brainres.2006.08.083 (In English)

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Graff, G. R., Gozal, D. (1999) Cardiorespiratory responses to interleukin-1β in adult rats: Role of nitric oxide, eicosanoids and glucocorticoids. Archives of Physiology and Biochemistry, vol. 107, no. 2, pp. 97–112. PMID: 10650342. DOI: 10.1076/apab.107.2.97.4344 (In English)

Hofstetter, A. O, Saha, S., Siljehav, V. et al. (2007) The induced prostaglandin E2 pathway is a key regulator of the respiratory response to infection and hypoxia in neonates. Proceedings of the National Academy of Sciences of the United States of America, vol. 104, no. 23, pp. 9894–9899. PMID: 17535900. DOI: 10.1073/pnas.0611468104. (In English)

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Olsson, A., Kayhan, G., Lagercrantz, H., Herlenius, E. (2003) IL-1β depresses respiration and anoxic survival via a prostaglandin-dependent pathway in neonatal rats. Pediatric Research, vol. 54, pp. 326–331. DOI: 10.1203/01.PDR.0000076665.62641.A2 (In English)

Paxinos, G., Watson, C. (1982) The rat brain in stereotaxic coordinates. Sydney: Academic Press, VII, 12 p., 71 bl. pl. (In English)

Published

2020-06-05

Issue

Section

Experimental articles