@article{1767, keywords = {Adolescent, Adult, Aged, BCG Vaccine, Child, Humans, Immunity, Interferon-gamma, Interleukin-10, leprosy, Leprosy, lepromatous, Leprosy, Tuberculoid, Lymphocyte Activation, Middle Aged, Mycobacterium leprae, Skin Tests, T-Lymphocytes, Tumor Necrosis Factor-alpha, Vaccination}, author = {Lima M C and Pereira G M and Rumjanek F D and Gomes H M and Duppre N and Sampaio E P and Alvim I M and Nery J A and Sarno E N and Pessolani M C}, title = {Immunological cytokine correlates of protective immunity and pathogenesis in leprosy.}, abstract = {

The in vitro production of interferon (IFN)-gamma, interleukin (IL)-5, tumour necrosis factor (TNF)-alpha and IL-10 by blood mononuclear cells in response to whole Mycobacterium leprae and polyclonal stimulii of 23 individuals, representing a variety of conditions in relation to exposure/susceptibility to M. leprae, was assayed. In most cases, healthy household contacts of newly diagnosed multibacillary leprosy patients, designated exposed household contacts (EC), showed low-to-undetectable in vitro IFN-gamma production in addition to substantial TNF-alpha production in response to M. leprae. In contrast, peripheral blood mononuclear cells from previously exposed contacts (R) regarded as resistant-to-leprosy released low-to-moderate levels of IFN-gamma together with a mixed cytokine profile resembling a T helper (Th)0-type response. TNF-alpha/IL-10 ratios in response to M. leprae and Concanavalin A were significantly higher in EC than in R contacts suggesting a role for the TNF-alpha/IL-10 ratio in restraining mycobacteria proliferation and spreading early in infection. The cytokine profiles of leprosy patients were taken as reference points. Post-treatment lepromatous leprosy patients secreted relatively high levels of IL-10 in response to M. leprae, whereas one self-cured tuberculoid leprosy patient produced simultaneously high levels of IFN-gamma and TNF-alpha. In addition, the quantitative changes in the cytokines released by peripheral blood mononuclear cells in EC contacts after Bacille Calmette-Guérin (BCG) vaccination were investigated. Vaccination induced amplification of IFN-gamma production with a concomitant decrease in TNF-alpha/IL-10 ratios that resembled the cytokine pattern observed in R contacts. IFN-gamma production was observed in response to both a cross-reactive antigen (Ag 85) and a M. leprae-specific protein (MMP-I), which attests to a BCG nonspecific stimulation of the immune system, thereby casting these antigens as likely candidates for inclusion in a subunit vaccine against leprosy. Finally, a model for protective x pathologic response to mycobacteria is presented.

}, year = {2000}, journal = {Scandinavian journal of immunology}, volume = {51}, pages = {419-28}, month = {2000 Apr}, issn = {0300-9475}, doi = {10.1046/j.1365-3083.2000.00703.x}, language = {eng}, }