2001
DOI: 10.1086/320699
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Combined Interleukin‐12 and Topical Chemotherapy for Established Leishmaniasis Drastically Reduces Tissue Parasitism and Relapses in Susceptible Mice

Abstract: The efficacy of the association of paromomycin sulfate (PA) with recombinant (r) interleukin (IL)-12 was investigated by topical treatment of BALB/c mice infected with Leishmania major that displayed fully developed cutaneous lesions. Although healing was observed in PA-treated groups, lesions recurred in 100% of these animals 70 days after treatment. In contrast, lesions were absent in a high proportion of PA- and rIL-12-treated mice 120 days after treatment. The PA/rIL-12-treated mice had a switch in cytokin… Show more

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Cited by 12 publications
(7 citation statements)
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References 38 publications
(47 reference statements)
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“…Similar therapeutic and prophylactic effects were observed with a combination regimen of PM and recombinant IL-12 against C. parvum, probably through activation of IFN-␥ production (19). This combination regimen was also found to be effective against established L. major infection, further inhibiting disease relapse in susceptible mice (16). The present study showed that PC-SA at a molar ratio of 7:2 significantly enhanced the levels of IL-12, IFN-␥, and NO and reduced significantly not only IL-10 but also TGF-␤, corroborating our previous observations (7).…”
Section: Discussionsupporting
confidence: 91%
“…Similar therapeutic and prophylactic effects were observed with a combination regimen of PM and recombinant IL-12 against C. parvum, probably through activation of IFN-␥ production (19). This combination regimen was also found to be effective against established L. major infection, further inhibiting disease relapse in susceptible mice (16). The present study showed that PC-SA at a molar ratio of 7:2 significantly enhanced the levels of IL-12, IFN-␥, and NO and reduced significantly not only IL-10 but also TGF-␤, corroborating our previous observations (7).…”
Section: Discussionsupporting
confidence: 91%
“…The A2 proteins are composed predominantly of multiple copies of a 10-amino-acid repeat, and depending on the number of repeats within each protein, the protein size may range from 45 to 100 kDa (38). Karyotype analysis, performed with a panel of samples representative of different Leishmania species, revealed that A2 genes are conserved in species of the L. donovani complex and the L. mexicana complex (10). Recently, it was demonstrated that immunization with A2, as protein or DNA, protects against L. donovani infection (13,14).…”
mentioning
confidence: 99%
“…Splenocyte cultures and cytokine assays were performed as described previously (10). Briefly, single-cell preparations from spleen tissue were plated in duplicate in 24-well plates (Nunc) at 2 ϫ 10 6 cells/ml.…”
mentioning
confidence: 99%
“…In contrast, lesions were absent in a high proportion of PAand rIL-12-treated mice, even 120 days after treatment and this was associated with reductions in parasite load, dissemination of parasites and inflammation. The combination of PA and rIL-12 induced a switch from high IL-4 and low IFN-c levels to low IL-4 and high IFN-c levels (Fernandes et al 2001).…”
Section: Interleukin-12mentioning
confidence: 94%