PMID- 20102417 OWN - NLM STAT- MEDLINE DCOM- 20100709 LR - 20211020 IS - 1365-2567 (Electronic) IS - 0019-2805 (Print) IS - 0019-2805 (Linking) VI - 130 IP - 2 DP - 2010 Jun TI - Evaluation of localized and systemic immune responses in cutaneous leishmaniasis caused by Leishmania tropica: interleukin-8, monocyte chemotactic protein-1 and nitric oxide are major regulatory factors. PG - 193-201 LID - 10.1111/j.1365-2567.2009.03223.x [doi] AB - We have established Leishmania tropica as the causative agent of cutaneous leishmaniasis (CL) in the region of India where the disease is endemic. The association between localized and circulating levels of immune-determinants in CL patients was evaluated. Reverse transcription-polymerase chain reaction analysis revealed up-regulation of interferon-gamma (IFN-gamma), interleukin (IL)-1beta, IL-8, tumour necrosis factor-alpha (TNF-alpha), IL-10 and IL-4 in dermal lesions at the pretreatment stage (n = 31) compared with healthy controls (P < 0.001) and a significant down-regulation after treatment (n = 14, P < 0.05). The results indicated that an unfavourable clinical outcome in CL was not related to an inadequate T helper 1 (Th1) cell response, but rather to impairment in multiple immune functions. Comparative assessment of treatment regimes with rifampicin (RFM) or sodium antimony gluconate (SAG) revealed tissue cytokine levels to be significantly reduced after treatment with RFM (P < 0.005), while no significant decrease was evident in the levels of IFN-gamma, TNF-alpha and IL-10 (P > 0.05) as a result of treatment with SAG. Increased transcripts of monocyte chemoattractant protein-1 (MCP-1) (P < 0.001) and inducible nitric oxide synthase (iNOS) (P < 0.05) were evident before treatment in tissue lesions and remained high after treatment. Immunohistochemistry demonstrated strong expression of myeloperoxidase (MPO) and IL-8, and moderate expression of iNOS in dermal lesions. The expression levels of IL-8, MCP-1 and nitric oxide (NO) were high in patient sera before treatment, as determined using cytokine bead array and enzyme-linked immunosorbent assay (ELISA). At the post-treatment stage, the serum IL-8 levels had decreased; however, the levels of MCP-1 and NO remained high. These data suggest that IL-8 is an effector immune-determinant in the progression of CL, whereas NO facilitates the parasite killing by macrophages via MCP-1-mediated stimulation. FAU - Kumar, Rajesh AU - Kumar R AD - Institute of Pathology (ICMR), Safdarjung Hospital Campus, New Delhi. FAU - Bumb, Ram A AU - Bumb RA FAU - Salotra, Poonam AU - Salotra P LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20100122 PL - England TA - Immunology JT - Immunology JID - 0374672 RN - 0 (Antiprotozoal Agents) RN - 0 (CCL2 protein, human) RN - 0 (CXCL8 protein, human) RN - 0 (Chemokine CCL2) RN - 0 (IL10 protein, human) RN - 0 (IL4 protein, human) RN - 0 (Interleukin-8) RN - 0 (Nucleic Acid Synthesis Inhibitors) RN - 0 (Tumor Necrosis Factor-alpha) RN - 130068-27-8 (Interleukin-10) RN - 207137-56-2 (Interleukin-4) RN - 31C4KY9ESH (Nitric Oxide) RN - 82115-62-6 (Interferon-gamma) RN - EC 1.11.1.7 (Peroxidase) RN - EC 1.14.13.39 (NOS2 protein, human) RN - EC 1.14.13.39 (Nitric Oxide Synthase Type II) RN - V083S0159D (Antimony Sodium Gluconate) RN - VJT6J7R4TR (Rifampin) SB - IM MH - Adolescent MH - Adult MH - Antimony Sodium Gluconate/administration & dosage MH - Antiprotozoal Agents/administration & dosage MH - Chemokine CCL2/blood/*immunology MH - Child MH - Child, Preschool MH - Female MH - Humans MH - India/epidemiology MH - Interferon-gamma/blood/immunology MH - Interleukin-10/blood/immunology MH - Interleukin-4/blood/immunology MH - Interleukin-8/blood/*immunology MH - Leishmania tropica/*immunology/metabolism MH - Leishmaniasis, Cutaneous/blood/drug therapy/epidemiology/*immunology MH - Macrophages/*immunology/metabolism/pathology MH - Male MH - Middle Aged MH - Nitric Oxide/blood/immunology MH - Nitric Oxide Synthase Type II/biosynthesis/immunology MH - Nucleic Acid Synthesis Inhibitors/administration & dosage MH - Peroxidase/biosynthesis/immunology MH - Retrospective Studies MH - Rifampin/administration & dosage MH - Th1 Cells/immunology/metabolism/pathology MH - Tumor Necrosis Factor-alpha/blood/immunology MH - Up-Regulation/drug effects/*immunology PMC - PMC2878464 EDAT- 2010/01/28 06:00 MHDA- 2010/07/10 06:00 PMCR- 2011/06/01 CRDT- 2010/01/28 06:00 PHST- 2010/01/28 06:00 [entrez] PHST- 2010/01/28 06:00 [pubmed] PHST- 2010/07/10 06:00 [medline] PHST- 2011/06/01 00:00 [pmc-release] AID - IMM3223 [pii] AID - 10.1111/j.1365-2567.2009.03223.x [doi] PST - ppublish SO - Immunology. 2010 Jun;130(2):193-201. doi: 10.1111/j.1365-2567.2009.03223.x. Epub 2010 Jan 22.