Detection of circulant tumor necrosis factor-alpha, soluble tumor necrosis factor p75 and interferon-gamma in Brazilian patients with dengue fever and dengue hemorrhagic fever.

Pro-inflammatory cytokines are believed to play an important role in the pathogenesis of dengue infection. This study reports cytokine levels in a total of 54 patients examined in Recife, State of Pernambuco, Brazil. Five out of eight patients who had hemorrhagic manifestations presented tumor necrosis factor-alpha (TNF-alpha) levels in sera which were statistically higher than those recorded for controls. In contrast, only one out of 16 patients with mild manifestations had elevated TNF-alpha levels. The levels of interleukin-6 (IL), IL-1beta tested in 24 samples and IL-12 in 30 samples were not significantly increased. Interferon-g was present in 10 out of 30 patients with dengue. The data support the concept that the increased level of TNF-alpha is related to the severity of the disease. Soluble TNF receptor p75 was found in most patients but it is unlikely to be related to severity since it was found with an equivalent frequency and levels in 15 patients with dengue fever and another 15 with dengue hemorrhagic fever.

Nitric oxide production by murine peritoneal macrophages in vitro and in vivo treated with Phyllanthus tenellus extracts.

Phyllanthus spp. are used traditionally for the treatment of viral, bacterial and parasitic infections. Macrophages may play a central role in innate and adaptive response against several infections. Nitric oxide (NO) can be induced during macrophage activation and may exert antimicrobial activity inhibiting the replication of several viruses or parasites. In the present study, we investigated the immunomodulatory role, both in vitro and in vivo, of aqueous extracts of fresh and dried Phyllanthus tenellus as well as an acetone/water extract of the dried plant. NO production by mouse peritoneal macrophages was detected in culture supernatants. Our results demonstrated that: (1) in vitro, a concentration of 100 microg/ml fresh extract stimulated significantly (P< or =0.05) NO production in all assays and the optimal production was achieved at 48-h incubation; (2) 10 and 50 mg/kg fresh extract injected twice intraperitonealy primed macrophages in vivo. Priming was detected by in vitro addition of a second stimulus with 100 microg/ml extract of the fresh plant. Thus, P. tenellus was able to pre-activate macrophages in vivo, and induce full activation in vitro. Further studies should be carried out to better evaluate the optimal dose schedules in terms of time/response for obtaining antiviral or other antimicrobial activity without host damage.