Proceedings of The Physiological Society
Puerto de la Cruz, Tenerife (2003) J Physiol 548P, P168
Kinetics of procalcitonin in neutropaenic rats after bacterial and viral fevers
M.L. Ojeda, R. Maldonado, E. Tavares, D. Chbihi, A. Fernández-Alonso and F.J. Miñano
Unidad de Investigación, División de Farmacología Experimental y Clínica, Hospital de Valme, Facultad de Medicina, Universidad de Sevilla, Ctra de Cádiz s/n, Sevilla, 41014, Spain
Procalcitonin (PCT) concentration increases in bacterial infections but remains low in viral infections. Studies to date have demonstrated that PCT is synthesized and release in response to appropiate stimuli in the face of immunosuppression and leukopaenia.
The purpose of this study was to investigate the dynamics of PCT and fever in a neutropaenic rat model of gram-negative (lipopolysaccharide, LPS) and virus (polyinosinic-polycytidylic acid, poly I:C) sepsis that mimics the series of pathophysiological events that may accompany the administration of cytoreductive chemotherapy in cancer patients.
Male Wistar rats were used (weighing 250-275 g; Charles River Laboratory, Barcelona, Spain). All of the experimental procedures were performed following guidelines from the European Union (86/609/EU) and Spanish regulations (BOE/67:8509/1988) for the use of laboratory animals in chronic experiments. Body temperature (Tb) (± 0.1 °C) was measured by biotelemetry using transmitters (Mini Mitter, Sunriver, OR, USA) implanted intraperitoneally (I.P.) at least 7 days before the onset of experimentation, the rats were anaesthetised with a mixture of ketamine and xylazine I.P. All drugs were injected I.P. (Miñano et al. 1996).
Neutropaenia (< 50 mm3) was induced by injecting a first dose of cyclophosphamide (150 mg kg-1) and a second one (50 mg kg-1) at day 3. LPS (50 µg kg-1), poly I:C (100 µg kg-1) or an equivalent volume of pyrogen-free saline were administered 1 day after the second dose of cyclophosphamide (Bhattacharjee et al. 1994). Serum PCT levels were measured by immunoluminometric assay with a sensitivity of 0.1 ng ml-1.
Intraperitoneal injection of either LPS or poly I:C produced fever of greater magnitude in neutropenic animals. The febrile response induced by LPS was significantly higher than that induced by poly I:C. Time-kinetics studies demonstrated that the production of PCT was markedly increased at 8 h after LPS challenge in non-immunosuppessed animals and at 8 h after poly I:C challenge in neutropenic rats.
These results confirm that PCT is a well-known tool for detection of bacterial gram-negative fevers in immunocompetent animals. However, in contrast to normal rats, PCT was significantly increased during fever induced by poly I:C in neutropaenic rats. Finally, present data suggest that different cellular and humoral mechanisms, which may have important therapeutic implications, are involved in the development of a febrile response triggered by a bacterial and viral infection in normal and neutropenic animals.
Where applicable, experiments conform with Society ethical requirements