Efficacy of curcumin therapy against Angiostrongylus cantonensis-induced eosinophilic meningitis.

Angiostrongylus cantonensis can invade the central nervous system, leading to human eosinophilic meningitis or eosinophilic meningoencephalitis. Curcumin is a natural product which has the effects of anti-inflammation, anti-oxidation and anti-carcinogensis, while the administration of curcumin has been reported to possibly relieve the symptoms of meningitis. The present study tested the potential efficacy of curcumin in A. cantonensis-induced eosinophilic meningitis of BALB/c mice. Assay indicators for the therapeutic effect included the larvicidal effect, eosinophil counts and matrix metalloproteinase-9 (MMP-9) activity in angiostrongyliasis. Eosinophils were mildly reduced in treatment groups compared with infected-untreated mice. However, there were no significant differences in larvicidal effects or MMP-9 activity. This study suggests that anti-inflammatory treatment with curcumin alone has low efficacy, but the treatment does not interfere with MMP-9 expression and is not useful for larvicidal effects. The possible reasons include low curcumin across the blood-brain barrier and also those larvae that survive stimulate MMP-9 production, which promotes blood-brain barrier damage, with leukocytes then crossing the blood-brain barrier to cause meningitis. Further studies will be required to test these possibilities.

Differential expression of inducible nitric oxide synthase gene by alveolar and peritoneal macrophages in lipopolysaccharide-hyporesponsive C3H/HeJ mice.

In lipopolysaccharide (LPS)-hyporesponsive C3H/HeJ mice, alveolar macrophages (AMphi) produce much more tumour necrosis factor-alpha than peritoneal macrophages (PMphi) when stimulated with LPS (10 microgram/ml), but the induction of inducible nitric oxide synthase (iNOS) gene expression and production of nitric oxide (NO) in AMphi are not found. In the present study, we determined the induction of iNOS gene expression, using semi-quantitative reverse transcription-polymerase chain reaction, and the release of NO in AMphi and PMphi from C3H/HeJ and C3H/HeN mice. The results showed the induction of iNOS mRNA accumulation in a dose-dependent manner by LPS alone or in combination with interferon-gamma in both macrophages. The effects of the stimuli on iNOS gene expression and NO production were significantly higher in AMphi than in the PMphi of C3H/HeJ mice. The response of macrophages from C3H/HeN mice was similar to those from C3H/HeJ mice, but the difference of iNOS gene expression between AMphi and PMphi in C3H/HeN mice was not as striking as in C3H/HeJ mice. The results show that the iNOS gene expression and NO production were activated differently in AMphi and PMphi and suggest that the functional properties of macrophages isolated from distinct origins are different.