Neuroimmune interaction in cutaneous leishmaniasis
Author: Ahmed, Ahmed Abdelaziz
Date: 1998-09-25
Location: Föreläsningssalen, Hudkliniken, Karolinska sjukhuset
Time: 9.00
Department: Inst för medicin, Solna / Dept of Medicine, Solna
Abstract
This study was conducted to ascertain how complex interactions between the immune and nervous systems are involved in the pathophysiology of cutaneous leishmaniasis (CL) caused by Leishmania (L.) major. The proinflammatory cytokines interleukin (IL)-1, IL-6 and also tumour necrosis factor, (TNF)-[alpha], were shown to affect the granulomatous response of murine and human CL. IL-1 participated in the initial phase of the granuloma, while IL-6 and TNF-[alpha] were involved in the initial, maintenance and possibly also the resolution phases. L. major affected the peripheral nervous system in the skin of the resistant mouse, C57BL/6, causing reversible degeneration of the nerve fibres during the early weeks following parasite inoculation. During a late stage following infection, regeneration of the nerves-particularly in the epidermis-was observed. It would therefore appear that in murine CL, the proinflammatory cytokines are involved both directly and indirectly in nerve degeneration and regeneration process.
In murine CL, nerve growth factor (NGF) concentrations in skin, secondary lymphoid organs and serum were differently expressed in the resistant, C57BL/6, and the susceptible, BALB/c, mouse. At 1 week post-infection, the resistant strain had elevated levels of NGF in all analysed organs and serum, whereas the susceptible mice showed no significant change. When studied late in the infection, resistant mice had increased levels of NGF in skin and lymphoid organs, but not the serum, whereas the susceptible strain had high concentrations of NGF both locally in the skin and in draining lymph nodes as well as in serum.
Significantly reduced concentrations of calcitonin gene-related peptide (CGRP) and neuropeptide Y (NPY) were found in the skin, secondary lymphoid organs and dorsal root ganglia (DRG) of L. major infected animals of both strains, compared with control animals, as early as 1 week post-infection, and throughout the study period. This reduction was progressive and more pronounced in the susceptible mice. Live L. major promastigotes showed a chemotactic activity for macrophages, whereas paraformaldehyde-killed promastigotes inhibited their migration. The sonicated form of the parasite was ineffective, as were both Leishmania surface protease gp63 and parasite culture supernatant. Somatostatin (SOM), substance P (SP) and NPY inhibited live L. major promastigote-induced macrophage migration, whereas CGRP and vasoactive intestinal peptide (VIP) stimulated it.
In the resistant mouse, SOM, CGRP and VIP stimulated promastigote induced splenocyte proliferation, whereas NPY inhibited it. In the susceptible mouse, SOM and CGRP inhibited this proliferation. Furthermore, SOM stimulated production of interferon (IFN)-[upsilon] by splenocytes from both mouse strains and IL-4 secretion by splenocytes in susceptible mice. CGRP, VIP and NPY all stimulated IFN-Y secretion by splenocytes in the susceptible mice. VIP also stimulated IL-4 production in susceptible strain splenocytes. Unexpectedly, SP was without effect. These findings indicate the involvement of a complex interaction between the immune and the peripheral nervous systems in the pathophysiology of CL caused by L. major.
In murine CL, nerve growth factor (NGF) concentrations in skin, secondary lymphoid organs and serum were differently expressed in the resistant, C57BL/6, and the susceptible, BALB/c, mouse. At 1 week post-infection, the resistant strain had elevated levels of NGF in all analysed organs and serum, whereas the susceptible mice showed no significant change. When studied late in the infection, resistant mice had increased levels of NGF in skin and lymphoid organs, but not the serum, whereas the susceptible strain had high concentrations of NGF both locally in the skin and in draining lymph nodes as well as in serum.
Significantly reduced concentrations of calcitonin gene-related peptide (CGRP) and neuropeptide Y (NPY) were found in the skin, secondary lymphoid organs and dorsal root ganglia (DRG) of L. major infected animals of both strains, compared with control animals, as early as 1 week post-infection, and throughout the study period. This reduction was progressive and more pronounced in the susceptible mice. Live L. major promastigotes showed a chemotactic activity for macrophages, whereas paraformaldehyde-killed promastigotes inhibited their migration. The sonicated form of the parasite was ineffective, as were both Leishmania surface protease gp63 and parasite culture supernatant. Somatostatin (SOM), substance P (SP) and NPY inhibited live L. major promastigote-induced macrophage migration, whereas CGRP and vasoactive intestinal peptide (VIP) stimulated it.
In the resistant mouse, SOM, CGRP and VIP stimulated promastigote induced splenocyte proliferation, whereas NPY inhibited it. In the susceptible mouse, SOM and CGRP inhibited this proliferation. Furthermore, SOM stimulated production of interferon (IFN)-[upsilon] by splenocytes from both mouse strains and IL-4 secretion by splenocytes in susceptible mice. CGRP, VIP and NPY all stimulated IFN-Y secretion by splenocytes in the susceptible mice. VIP also stimulated IL-4 production in susceptible strain splenocytes. Unexpectedly, SP was without effect. These findings indicate the involvement of a complex interaction between the immune and the peripheral nervous systems in the pathophysiology of CL caused by L. major.
Issue date: 1998-09-04
Publication year: 1998
ISBN: 99-2663794-9
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