Cytokines and the acute phase response in post-treatment reactive encephalopathy of Trypanosoma brucei brucei infected mice

Eckersall, P.D., Gow, J.W., McComb, C., Bradley, B., Rodgers, J., Murray, M. and Kennedy, P.G.E. (2001) Cytokines and the acute phase response in post-treatment reactive encephalopathy of Trypanosoma brucei brucei infected mice. Parasitology International, 50(1), pp. 15-26. (doi:10.1016/S1383-5769(00)00065-9)

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Abstract

Stimulation of the acute phase response during infection of mice with Trypanosoma brucei brucei (T. b. brucei) was investigated in an experimental model of the post-treatment reactive encephalopathy (PTRE), a common side-effect of anti-trypanosome therapy. Plasma levels of the acute phase proteins (APP), haptoglobin (Hp) and serum amyloid P (SAP) increased by day 7 post-infection, but by day 20 had fallen to an intermediate level. This was accompanied by induction of the cytokines, interleukin (IL)-6 and tumour necrosis factor-alpha (TNFalpha) in both liver and brain. Treatment of mice on day 21 with a subcurative dose of diminazene aceturate (Berenil), a procedure known to induce a mild PTRE, cleared the parasite from the circulation with plasma APP and liver expression of mRNA for IL-6 and TNFalpha returning to the levels in the controls. Cytokine mRNA for both IL-6 and TNFalpha was detected in the brains of animals with developing PTRE although TNFalpha was not significantly greater than in the control group. A further subcurative dose of Berenil, leading to a more severe PTRE, was associated with elevated serum concentrations of Hp and SAP, increased TNFalpha mRNA in the liver and detectable IL-6 and TNFalpha mRNA in the brain. mRNA for IL-1alpha was expressed in brain and liver samples from all animals. A severe PTRE caused a systemic acute phase response which was not apparent with a mild PTRE. The pattern of cytokine mRNA induction was similar following both drug treatments. However, the difference in APP production could be caused by a breakdown in the blood-brain barrier during severe PTRE allowing cytokine synthesised in the brain to enter the circulation and maintain a systemic response.

Item Type:Articles
Keywords:Trypanosoma brucei brucei, acute phase response, post-treatment reactive encephalopathy, haptoglobin, serum amyloid P, cytokines
Status:Published
Refereed:Yes
Glasgow Author(s) Enlighten ID:Eckersall, Professor David and Kennedy, Professor Peter and Murray, Professor Max
Authors: Eckersall, P.D., Gow, J.W., McComb, C., Bradley, B., Rodgers, J., Murray, M., and Kennedy, P.G.E.
College/School:College of Medical Veterinary and Life Sciences
College of Medical Veterinary and Life Sciences > Institute of Infection Immunity and Inflammation
Journal Name:Parasitology International
Publisher:Elsevier
ISSN:1383-5769
ISSN (Online):1873-0329

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