Cardiorespiratory responses to interleukin-1 beta in adult rats: Role of nitric oxide, eicosanoids and glucocorticoids

Interleukin-1 beta (IL-1 beta) receptors are abundantly expressed in brain stem regions involved in respiratory control. We hypothesized that systemic administration of IL-1 beta would increase ventilation ((V) over dot(E)), and that nitric oxide, eicosanoids, and glucocorticoid receptors would modu late IL-1 beta-induced cardioventilatory responses. Intravenous injections of three doses (37.5 ng kg(-1), 75 ng kg(-1) and 150 ng kg(-1)) of IL-1 bet a induced monophasic increases in ((V) over dot(E)), heart rate (HR), and b lood pressure (BP) which had a distinctly different onset and duration of a ction compared to IL-1 beta-induced body temperature elevations. Pre-treatm ent with the nitric oxide inhibitor L-NAME was associated with decreased pe ak (V) over dot(E) responses, without affecting the latency and duration of IL-1 beta. L-NAME also enhanced HR responses while pressor responses were attenuated. Eicosanoid inhibition with indomethacin resulted in markedly at tenuated (V) over dot responses. However, cardiovascular responses to IL-1 beta were not modified by indomethacin. In contrast, pre-treatment with dex amethasone, was not associated with any changes in the IL-1 beta-induced (V ) over dot(E), HR, or BP responses. We conclude that IL-1 beta increases of (V) over dot(E) are dose-dependent and are not time-locked with the pyrexi c response suggesting the possibility that distinct neural pathways may und erlie these responses. In addition, nitric oxide and eicosanoid-dependent m echanisms modulate IL-1 beta ventilatory effects.