Alanine Transaminase ; blood ; Alkaloids ; pharmacology ; Animals ; Aspartate Aminotransferases ; blood ; Carbon Tetrachloride ; Interleukin-10 ; analysis ; biosynthesis ; Liver Cirrhosis, Experimental ; drug therapy ; immunology ; Male ; Quinolizines ; Rats ; Rats, Wistar ; Tumor Necrosis Factor-alpha ; analysis ; biosynthesis

For treating Leishmania major infection in BALB/c mice, we used thalidomide in conjunction with glucantime. Groups of mice were challenged with 5 x 10(3) metacyclic promastigotes of L. major subcutaneously. A week after the challenge, drug treatment was started and continued for 12 days. Thalidomide was orally administrated 30 mg/kg/day and glucantime was administrated intraperitoneally (200 mg/kg/day). It was shown that the combined therapy is more effective than single therapies with each one of the drugs since the foot pad swelling in the group of mice received thalidomide and glucantime was significantly decreased (0.9 +/- 0.2 mm) compared to mice treated with either glucantime, thalidomide, or carrier alone (1.2 +/- 0.25, 1.4 +/- 0.3, and 1.7 +/- 0.27 mm, respectively). Cytokine study showed that the effect of thalidomide was not dependent on IL-12; however, it up-regulated IFN-gamma and down-regulated IL-10 production. Conclusively, thalidomide seems promising as a conjunctive therapy with antimony in murine model of visceral leishmaniasis.
Time Factors ; Thalidomide/pharmacology/*therapeutic use ; Organometallic Compounds/pharmacology/*therapeutic use ; Mice, Inbred BALB C ; Mice ; Meglumine/pharmacology/*therapeutic use ; Leishmaniasis, Visceral/*drug therapy/immunology ; Leishmania major/*drug effects ; Interleukin-12/analysis/biosynthesis ; Interleukin-10/analysis/biosynthesis ; Interferon Type II/analysis/biosynthesis/drug effects ; Immunosuppressive Agents/pharmacology/*therapeutic use ; Female ; Drug Therapy, Combination ; Disease Progression ; Disease Models, Animal ; Cells, Cultured ; Antiprotozoal Agents/pharmacology/*therapeutic use ; Animals

Several myeloid leukemia-derived cells have been reported to possess the ability to differentiate into dendritic cells (DC). MUTZ-3, a myeloid leukemia cell line, responds to GM-CSF, IL-4 and TNF-alpha, and acquires a phenotype similar to immature monocyte-derived DC (MoDC). In the present study, MUTZ-3-derived DC (MuDC) showed high level expression of HLA class II molecules, CD80 and CD86, and were able to function as potent antigen presenting cells as previously reported. Interestingly, MuDC maturation was induced by CD40-mediated stimulation, but not by LPS stimulation. We analyzed CCR1, CCR7 and Toll-like receptor (TLR) expressions in MuDC, and measured IL-10 and IL-12 production after maturation stimuli. Although MuDC expressed the mRNA for TLR4, a major component of the LPS receptor system, they did not show an enhanced level of CCR7 or cytokine production after LPS stimulation. In contrast, they responded to CD40 stimulation, which resulted in increased levels of CD83, CD86 and CCR7. Moreover, while LPSstimulated MoDC could potently stimulate NK cells in a DC-NK cell co-culture, LPS-stimulated MuDC failed to stimulate primary NK cells. Taken together, our findings suggest that, although MuDC express TLR4, unlike TNF-alpha and IL-1beta, LPS does not stimulate MuDC to acquire mature phenotypes, and they may have impaired activity to initiate innate immune response.
Antigens, CD40/metabolism/pharmacology ; Antigens, CD80/metabolism ; Antigens, CD86/metabolism ; Blotting, Western ; CD40 Ligand/metabolism/pharmacology ; Cell Differentiation ; Cell Line, Tumor ; Coculture Techniques ; Dendritic Cells/*drug effects/metabolism ; Enzyme-Linked Immunosorbent Assay ; Fluorescein-5-isothiocyanate ; Fluorescent Antibody Technique, Indirect ; Fluorescent Dyes ; Humans ; Interleukin-10/analysis/biosynthesis ; Interleukin-12/analysis/biosynthesis ; Killer Cells, Natural/metabolism ; Leukemia, Myeloid/*pathology ; Lipopolysaccharides/*pharmacology ; Mitogen-Activated Protein Kinase 3/metabolism ; RNA, Messenger/metabolism ; Research Support, Non-U.S. Gov't ; Reverse Transcriptase Polymerase Chain Reaction ; Toll-Like Receptor 4/metabolism ; Tumor Necrosis Factor-alpha/pharmacology ; p38 Mitogen-Activated Protein Kinases/metabolism