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

• Published in: Parasitology international 2001-03, Vol.50 (1), p.15-26
• Main Authors: Eckersall, P.David, Gow, John W, McComb, Christopher, Bradley, Barbara, Rodgers, Jean, Murray, Maxwell, Kennedy, Peter G.E
• Format: Article
• Language: English
• Subjects: Acute phase response; acute phase substances; Acute-Phase Proteins - metabolism; Acute-Phase Reaction; Animals; Cytokines; Cytokines - metabolism; Diminazene - analogs & derivatives; Diminazene - therapeutic use; Diminazene - toxicity; Disease Models, Animal; Encephalitis - etiology; Encephalitis - immunology; Female; Haptoglobin; Haptoglobins - metabolism; Mice; Parasitemia - parasitology; Post-treatment reactive encephalopathy; Reverse Transcriptase Polymerase Chain Reaction; RNA, Messenger - metabolism; serum amyloid; Serum amyloid P; Serum Amyloid P-Component - metabolism; Trypanocidal Agents - therapeutic use; Trypanocidal Agents - toxicity; Trypanosoma brucei; Trypanosoma brucei brucei; Trypanosoma brucei brucei - immunology; Trypanosomiasis, African - complications; Trypanosomiasis, African - drug therapy; Trypanosomiasis, African - immunology
• ISSN: 1383-5769; 1873-0329
• DOI: 10.1016/S1383-5769(00)00065-9

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-α (TNFα) 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 TNFα returning to the levels in the controls. Cytokine mRNA for both IL-6 and TNFα was detected in the brains of animals with developing PTRE although TNFα 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 TNFα mRNA in the liver and detectable IL-6 and TNFα mRNA in the brain. mRNA for IL-1α 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.