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-a (TNFa) 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 TNFa returning to the levels in the controls. Cytokine mRNA for both IL-6 and TNFa was detected in the brains of animals with developing PTRE although TNFa 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 TNFa mRNA in the liver and detectable IL-6 and TNFa mRNA in the brain. mRNA for IL-1a 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.
| Original language | English |
|---|---|
| Journal | Parasitology International |
| DOIs | |
| Publication status | Published - 1 Mar 2001 |
Fingerprint
Keywords
- cytokines
- acute phase response
- Trypanosoma brucei brucei
- post-treatment reactive encephalopathy
Cite this
}
Cytokines and the acute phase response in post-treatment reactive encephalopathy of Trypanosoma brucei brucei infected mice. / Eckersall, P. David; Gow, John W.; McComb, Christopher; Bradley, Barbara; Rodgers, Jean; Murray, Maxwell; Kennedy, Peter G.E.
In: Parasitology International, 01.03.2001.Research output: Contribution to journal › Article
TY - JOUR
T1 - Cytokines and the acute phase response in post-treatment reactive encephalopathy of Trypanosoma brucei brucei infected mice
AU - Eckersall, P. David
AU - Gow, John W.
AU - McComb, Christopher
AU - Bradley, Barbara
AU - Rodgers, Jean
AU - Murray, Maxwell
AU - Kennedy, Peter G.E.
N1 - <p>Originally published in: Parasitology International (2001), 50 (1), pp.15-26.</p>
PY - 2001/3/1
Y1 - 2001/3/1
N2 - 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-a (TNFa) 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 TNFa returning to the levels in the controls. Cytokine mRNA for both IL-6 and TNFa was detected in the brains of animals with developing PTRE although TNFa 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 TNFa mRNA in the liver and detectable IL-6 and TNFa mRNA in the brain. mRNA for IL-1a 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.
AB - 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-a (TNFa) 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 TNFa returning to the levels in the controls. Cytokine mRNA for both IL-6 and TNFa was detected in the brains of animals with developing PTRE although TNFa 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 TNFa mRNA in the liver and detectable IL-6 and TNFa mRNA in the brain. mRNA for IL-1a 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.
KW - cytokines
KW - acute phase response
KW - Trypanosoma brucei brucei
KW - post-treatment reactive encephalopathy
U2 - 10.1016/S1383-5769(00)00065-9
DO - 10.1016/S1383-5769(00)00065-9
M3 - Article
JO - Parasitology International
JF - Parasitology International
SN - 1383-5769
ER -