Differential expression of nerve growth factor in Leishmania major murine cutaneous leishmaniasis

The cross-talk between the immune and nervous systems is becoming an interesting field of research and there is accumulating evidence supporting this notion. In the present study we investigated the levels of nerve growth factor in a murine model of cutaneous leishmaniasis, using a two-site ELISA. Two strains of inbred mice were used for this purpose, namely BALB/c and C57BL/6, genetically susceptible and resistant, respectively, to infection with Leishmania major. This work demonstrates a difference in expression of nerve growth factor in the skin and secondary lymphoid organ microenvironment, as well as in the serum, between these mouse strains. The high nerve growth factor levels in the microenvironment seem to be important and possibly critical for the outcome of the disease. Compared with controls, the resistant strain, C57BL/6, expressed significantly increased nerve growth factor levels in the skin, secondary lymphoid organs and serum at 1 week post-infection, whereas the susceptible strain, BALB/c, showed no change in the skin and a slight increase in the lymphoid organs and serum at this time-point. These high nerve growth factor levels in the early stage of the disease, whether produced directly by the inflammatory cells or indirectly through its induction by other cytokines or both, might indicate a contribution of this neurotrophic factor to differentiation of naive T lymphocytes into either Th1 or Th2 subsets that fundamentally govern the disease outcome. The expression of significantly elevated nerve growth factor levels in the skin and lymphoid organs of C57BL/6 at the late studied time points might suggest a role for nerve growth factor in the resolution of the disease process, which is usually evident from 6 weeks post-infection in this model. The high nerve growth factor levels expressed in the skin, lymph nodes and serum of BALB/c at late stages of the disease may be explained as an attempt to counteract the progression and dissemination of the disease. This investigation adds further experimental evidence for an anti-inflammatory effect of nerve growth factor, possibly through its action as a link between the nervous and immune systems.