Correlation between nerve growth factor and tissue expression of IL-17 in leprosy.

Leprosy is a serious public health problem in peripheral and developing countries. Leprosy is a chronic infectious-contagious disease caused by the intracellular, bacillus Mycobacterium leprae, which causes tissue damage and demyelination of peripheral nerves. Recent studies have demonstrated the participation of new subtype's cytokines profile in the inflammatory response of leprosy. Since nerve functions are affected by inflammatory response during the course of leprosy, changes in the production of NGF and its receptor (NGF R) may be directly associated with disability and sensory loss. Skin biopsies were collected and submitted to immunohistochemistry using specific antibodies to IL-17, NGF and NGF R. Quantitative analysis of NGF, NGFR and IL-17 immunostaining showed a significant difference between the clinical forms, with higher expression of NGF and NGFR in lepromatous leprosy and IL-17 in tuberculoid leprosy. The present study showed that IL-17, in addition to stimulating an inflammatory response, negatively regulates the action of NGF and NGF R in the polar forms of the disease.

Administration of Mycobacterium leprae rHsp65 aggravates experimental autoimmune uveitis in mice.

The 60 kDa heat shock protein family, Hsp60, constitutes an abundant and highly conserved class of molecules that are highly expressed in chronic-inflammatory and autoimmune processes. Experimental autoimmune uveitis [EAU] is a T cell mediated intraocular inflammatory disease that resembles human uveitis. Mycobacterial and homologous Hsp60 peptides induces uveitis in rats, however their participation in aggravating the disease is poorly known. We here evaluate the effects of the Mycobacterium leprae Hsp65 in the development/progression of EAU and the autoimmune response against the eye through the induction of the endogenous disequilibrium by enhancing the entropy of the immunobiological system with the addition of homologous Hsp. B10.RIII mice were immunized subcutaneously with interphotoreceptor retinoid-binding protein [IRBP], followed by intraperitoneally inoculation of M. leprae recombinant Hsp65 [rHsp65]. We evaluated the proliferative response, cytokine production and the percentage of CD4(+)IL-17(+), CD4(+)IFN-gamma(+) and CD4(+)Foxp3(+) cells ex vivo, by flow cytometry. Disease severity was determined by eye histological examination and serum levels of anti-IRBP and anti-Hsp60/65 measured by ELISA. EAU scores increased in the Hsp65 group and were associated with an expansion of CD4(+)IFN-gamma(+) and CD4(+)IL-17(+) T cells, corroborating with higher levels of IFN-gamma. Our data indicate that rHsp65 is one of the managers with a significant impact over the immune response during autoimmunity, skewing it to a pathogenic state, promoting both Th1 and Th17 commitment. It seems comprehensible that the specificity and primary function of Hsp60 molecules can be considered as a potential pathogenic factor acting as a whistleblower announcing chronic-inflammatory diseases progression.