RESUMO
The secretion of interferon-gamma (IFN-gamma), interleukin-2 (IL-2), IL-4, IL-5, and IL-10 by antigen-stimulated lymph node cells, eosinophil maturation, and the antibody isotypes produced were examined during intraperitoneal infection of susceptible (B10.A) and resistant (A/Sn) mice with Paracoccidioides brasiliensis. Lymph node cells from resistant mice produced early and sustained levels of IFN-gamma and IL-2, whereas susceptible animals secreted low to undetectable amounts of these type 1 cytokines. Both mouse strains presented late and transient production of IL-4, whereas IL-10 was produced constantly throughout the course of disease. Resistant animals produced increasing levels of IL-5 in the chronic phase of the infection (from the eighth week on), whereas susceptible mice showed two peaks of IL-5 production, at the first and twelfth weeks after infection. Only the susceptible strain presented medullary and splenic eosinophilia concomitant with the raised IL-5 production. In resistant mice, the levels of IgG2a antibodies were significantly higher than those observed in susceptible mice, which preferentially secreted IgG2b and IgA isotypes. Taken together, these results demonstrate that a sustained production of IFN-gamma and IL-2 and a predominant secretion of IgG2a antibodies are associated with resistance to P. brasiliensis. In contrast, the production of low levels of IFN-gamma, early secretion of high levels of IL-5 and IL-10, eosinophilia, and a preferential secretion of IgG2b and IgA isotypes characterize the progressive disease in susceptible animals.
Assuntos
Interferon gama/deficiência , Interleucinas/biossíntese , Paracoccidioides , Paracoccidioidomicose/imunologia , Células Th1/imunologia , Animais , Anticorpos Antifúngicos/biossíntese , Linfócitos B/imunologia , Medula Óssea/patologia , Eosinofilia/etiologia , Eosinofilia/imunologia , Feminino , Predisposição Genética para Doença , Imunidade Celular , Imunidade Inata , Imunoglobulina A/biossíntese , Imunoglobulina G/biossíntese , Interferon gama/biossíntese , Interferon gama/genética , Interleucina-2/biossíntese , Interleucina-2/genética , Interleucina-5/biossíntese , Interleucina-5/genética , Interleucinas/genética , Interleucinas/metabolismo , Linfonodos/imunologia , Ativação Linfocitária , Ativação de Macrófagos , Camundongos , Camundongos Endogâmicos A , Paracoccidioidomicose/genética , Paracoccidioidomicose/patologia , Cavidade Peritoneal/citologia , Baço/patologia , Células Th1/metabolismo , Células Th2/imunologiaRESUMO
OBJECTIVE AND DESIGN: To determine the alpha-2-macroglobulin (alpha2M) levels in mice during acute and chronic inflammatory responses. MATERIALS AND METHODS: Inflammation was induced by one of the following stimuli: carrageenin, zymosan, lipopolysacharide, thioglycollate, bacilli Calmette Guerin, PPD (in pre-immunized and non-immunized animals) and tumor cells. The concentration of alpha2M was determined in plasma or peritoneal liquid by electroimmunoassay. RESULTS: In all the treatments employed, the plasma levels of alpha2M were higher than in untreated animals. This increase varied from 9%, 24 h after injection up a maximum of 66% 72 h post-injection. When compared to animals injected only with saline, the increases were significant 48 h after treatment with either zymosan or LPS, and 72 h after treatment with either thioglycollate or carrageenin. Treatment with BCG triggers an increase in alpha2M levels after 24 h (18.60%) and 48 h (27.90%). Immunized mice presented higher levels of this protein than non-immunized animals after challenge with PPD. The growth of Ehrlich tumor cells in the peritoneal cavity was directly correlated with the local levels of alpha2M which increased 3.5 fold, 10 days after injection. CONCLUSIONS: These results strongly indicate that in mice, the concentration of alpha2M can increase during acute and chronic inflammatory reactions with kinetics dependent on the particular kind of inflammatory agent.