The cascade of fever production in influenza was studied. To analyse fever production in a murine model, we selected DBA/2 mice that have the highest susceptibility in fibrile responses among seven mouse strains. Intranasal influenza infection- and interferon (IFN)-induced fever production was studied in this mouse model. Fever was induced prominently on day 2 after influenza infection and IFN activity was also increased in serum. Only the level of interleukin (IL)-1 alpha, an endogenous pyrogen, rose markedly in serum among cytokines (IL-1 alpha, IL-2, IFN-gamma, and tumor necrosis factor-alpha) examined. Fever was induced 14 hr after intraperitoneal IFN-alpha treatment and IL-1 alpha level rose significantly in the serum of the IFN-alpha-treated mice as compared with that of untreated mice. Fever production was significantly suppressed by treatment with anti-IFN-alpha/beta or anti-IL-1 alpha antibody in infected mice and the former significantly suppressed responsive IL-1 alpha production, indicating that elevated IFN activity induced IL-1 alpha production and subsequently fever production in infected mice. The activity of cyclooxygenase (COX) that produces prostaglandin (PG)E2 was significantly augmented in the brain of infected mice on day 2 after infection. Fever production was suppressed by the inhibition of COX activity with aspirin, although IL-1 alpha level was maintained at the elevated level. Therefore, influenza infection in mice turned on the following cascade for fever induction: IFN production, IL-1 alpha production, elevated COX activity, and PGE2 production. We elucidated the relationship among IFN activity, IL-1 alpha production and COX activity and demonstrated the cascade of fever production in influenza infection.
BackgroundSecondary myeloid neoplasms comprise a group of secondary diseases following exposure to myelotoxic agents or due to congenital diseases. The improvement of anticancer agents and immunosuppressive drugs seem to be associated with an increased incidence of secondary myeloid neoplasms. Karyotyping of bone marrow is essential for diagnosis and prognosis. Previous use of alkylating agents and radiation are associated with clonal abnormalities such as recurrent unbalanced -5/5q-, -7/7q- and complex karyotypes, whereas topoisomerase-II inhibitors lead to changes such as the balanced 11q23 rearrangement, t(8;21), t(15;17) and inv(16).ObjectiveTo study the clinical and cytogenetic data of patients with secondary myeloid neoplasms who took antineoplastic and/or immunosuppressive drugs or progressed from aplastic anemia.MethodsThe clinical and cytogenetic characteristics of 42 patients diagnosed with secondary myeloid neoplasms in one institution were retrospectively evaluated. Of these, 25, 11 and 6 patients had had oncological diseases, aplastic anemia and other diseases, respectively. Conventional cytogenetic and FISH analyses were performed for monosomy 7.ResultsThe cytogenetic study was conclusive in 32 cases with 84.4% of clonal abnormalities. Monosomy 7 and complex karyotypes were present in 44.4% and 37%, respectively. A high prevalence of unbalanced abnormalities (96.3%) was observed. Monosomy 7 was more prevalent in patients with myelodysplastic syndromes/myeloid neoplasms after aplastic anemia (66.6%). The median survival after diagnosis of myeloid neoplasms was only 5.7 months. Normal cytogenetics was associated to better survival (p-value = 0.03). There was a slightly worse trend of survival for patients with complex karyotypes (p-value = 0.057). Abnormal karyotype was an independent risk factor for poor survival (p-value = 0.012).ConclusionThis study enhances the importance of cytogenetic analysis of patients at the time of diagnosis of secondary myeloid neoplasms.
Eighty-six newly diagnosed multiple myeloma (MM) patients from a public hospital of São Paulo (Brazil) were evaluated by cIg-FISH for the presence of del(13)(q14), t(4;14)(p16.3;q32) and del(17)(p13). These abnormalities were observed in 46.5, 9.3, and 7.0% of the patients, respectively. In order to identify the possible role of del(13)(q14) in the physiopathology of MM, we investigated the association between this abnormality and the proliferative and apoptotic indexes of plasma cells. When cases demonstrating t(4;14)(p16.3;q32) and del(17)(p13) were excluded from the analysis, we observed a trend towards a positive correlation between the proportion of cells carrying del(13)(q14) and plasma cell proliferation, determined by Ki-67 expression (r = 0.23, P = 0.06). On the other hand, no correlation between the proportion of cells carrying del(13)(q14) and apoptosis, determined by annexin-V staining, was detected (r = 0.05, P = 0.69). In general, patients carrying del(13)(q14) did not have lower survival than patients without del(13)(q14) (P = 0.15), but patients with more than 80% of cells carrying del(13)(q14) showed a lower overall survival (P = 0.033). These results suggest that, when del(13)(q14) is observed in a high proportion of malignant cells, it may have a role in determining MM prognosis. Another finding was a statistically significant lower overall survival of patients with t(4;14)(p16.3;q32) (P = 0.026). In the present study, almost half the patients with t(4;14)(p16.3;q32) died just after diagnosis, before starting treatment. This fact suggests that, in São Paulo, there may be even more patients with this chromosomal abnormality, but they probably die before being diagnosed due to unfavorable socioeconomic conditions. This could explain the low prevalence of this chromosomal abnormality observed in the present study.
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