The aim of the present study was to investigate the kinetics of humoral and cellular responses during leptospirosis. We observed that the presence of tumor necrosis factor-alpha (TNF-alpha) and interleukin-6 (IL-6) was associated with antibody production and bacterial recovery, and the compromising of both TNF-alpha and IL-6 in the immunopathogenesis of leptospirosis during an experimental infection of BALB/c mice inoculated with Leptospira interrogans serovar Canicola was verified. Results showed higher levels of TNF-alpha and IL-6 in the initial phase of infection, in which the greatest bacterial clearance was observed. However, when the bacterial recovery was compared with the kinetics of the production of antibodies, the results revealed a kinetics proportionally inverted to antibody production. This fact may be related to some inhibitory factor which could be responsible for the selective suppression of the cellular immune response. We concluded that during leptospirosis there was a greater mobilization of the cellular immune response activity, mainly in the initial phase of the infectious process, for posterior involvement of the humoral response, and that both TNF-alpha and IL-6 could be associated with the immunopathogenesis of the disease.

Immune response to leptospirosis is mainly humorally mediated, and involves opsonization of leptospires for phagocytosis by macrophages and neutrophils. However, some aspects are still unknown. For a more detailed analysis of the cellular immune response to leptospirosis infection, trials were carried out in order to determine the hydrogen peroxide and nitric oxide (H2O2 and NO) production stimulated or not by Interferon-gamma. The participation of some specific cytokines, such as Tumor Necrosis Factor-alpha (TNF-alpha); Interferon-gamma (IFN-gamma); Interleukin-6 (IL-6); and Interleukin-4 (IL-4), in the immunopathology of this infection was also investigated. For this purpose, we analyzed the supernatant from peritoneal macrophage cell culture and the splenic cells of mice genetically selected as High (H) and Low (L) antibody producers, and inbred Balb/c mice infected with Leptospira interrogans serovar icterohaemorrhagiae. The IL-6 production varied from release peaks to inhibition in H, L, and Balb/c mice. Similar behavior was observed for IL-4, produced only by H and Balb/c mice. The three strains presented constant and elevated production of TNF-alpha until day 14, suggesting its effective participation in the initial phase of the infection. Meanwhile, all the three strains presented a constant and irregular IFN-gamma production, with release peaks between the 7th and 14th days in L mice. The H and Balb/c mice strains presented a higher tendency to Th2 response pattern, whereas L mice tended towards Th1 response.