Arginase activity is associated with fibrosis in experimental infection with Taenia crassiceps, but does not play a major role in resistance to infection.

Murine infection with Taenia crassiceps cysticerci is used as an experimental model for human and animal cysticercosis. In this infection parasites can be found associated with an inflammatory infiltrate enriched with macrophages. Experimental evidence exists supporting a role for either NO-producing classically activated (CAMΦ) or arginase- and CD301-expressing alternatively activated macrophages (AAMΦ) in T. crassiceps resistance. In both cell types, arginine is utilized as an important mediator in macrophage effector functions. To investigate whether there is an association between arginine availability, susceptibility to T. crassiceps and other parameters such as fibrosis, BALB/c mice were infected intraperitoneally with cysticerci and treated daily with the arginase inhibitor nor-NOHA or supplemented with l-arginine and followed for eight weeks. The numbers and developmental stages of parasites were evaluated as well as the presence of CD301+ AAMΦ, arginase activity and collagen deposition in the peritoneal membrane. Treatment with the arginase inhibitor or supplementation with l-arginine did not change the parasitic load or profile of the infection. However, the arginase inhibitor significantly decreased the deposition of collagen. These results suggest that arginase activity does not interfere with parasite control during experimental infection with T. crassiceps, but it is important for fibrosis in cysticercosis.

Electroacupuncture at the ST36 acupoint increases interleukin-4 responsiveness in macrophages, generation of alternatively activated macrophages and susceptibility to Leishmania major infection.

BACKGROUND: Electroacupuncture (EA) has been used to treat inflammatory diseases. Alternatively activated macrophages (AAMo) stimulated by cytokines such as interleukin (IL)-4, IL-10 and IL-13 are anti-inflammatory and mildly microbicidal. This study aimed to evaluate whether EA at the Zusanli acupoint (ST36) would change the profile of healthy murine macrophages, particularly the generation of AAMo and susceptibility to Leishmania major infection. METHODS: BALB/c mice were treated with EA (15/30 Hz) at the ST36 acupoint for 20 min/d for 5 d. After the final EA session, the mice were euthanized and their peritoneal cells were harvested and counted for determination of arginase activity, nitric oxide (NO) production and microbicidal activity after culture in the presence or absence of IL-4, interferon-γ (IFNγ) or lipopolysaccharide (LPS) or both IFNγ and LPS. Twelve mice were infected with L. major promastigotes into the footpads after the final EA session and the infection course was monitored. RESULTS: Peritoneal cells freshly obtained from EA-treated mice had similar arginase and microbicidal activities to cells from sham-treated mice. After culture with IL-4, cells from EA-treated mice exhibited significant increases in the arginase activity (sham: 58 ± 11.3 vs. EA: 80.7 ± 4.6%, P = 0.025) and number of parasites/infected cell (sham: 2.5 ± 0.4 vs. EA: 4.3 ± 0.8 cells, P = 0.007). The NO production was lower in cells from EA-treated mice cultured in the presence of a combination of IFNγ and LPS (sham: 31.6 ± 6.5 vs. EA: 22.3 ± 2.1 µM, P = 0.025). The lesion size in mice infected with L. major promastigotes was larger in EA-treated mice (sham: 3.26 ± 0.29 vs. EA: 2.23 ± 0.4 mm, P = 0.039). CONCLUSION: EA at the ST36 acupoint increases IL-4 responsiveness in macrophages, Generation of AAMo and susceptibility to L. major infection.