RESUMO
Nitric oxide (NO) is a radical molecule that not only serves as a vasodilator and neurotransmitter but also acts as a cytotoxic effector molecule of the immune system. The inducible enzyme making NO, inducible NO synthase (iNOS), is transcriptionally activated by IFN-gamma and TNF-alpha, cytokines which are produced during viral infection. We show that iNOS is induced in mice infected with the Coxsackie B3 virus. Macrophages expressing iNOS are identified in the hearts and spleens of infected animals with an antibody raised against iNOS. Infected mice have increased titers of virus and a higher mortality when fed NOS inhibitors. Thus, viral infection induces iNOS in vivo, and NO inhibits viral replication. NO is a novel, nonspecific immune defense against viruses in vivo.
Assuntos
Infecções por Coxsackievirus/fisiopatologia , Enterovirus Humano B/fisiologia , Miocardite/fisiopatologia , Miocardite/virologia , Óxido Nítrico Sintase/biossíntese , Óxido Nítrico/fisiologia , Replicação Viral , Sequência de Aminoácidos , Animais , Anticorpos , Arginina/análogos & derivados , Arginina/toxicidade , Linhagem Celular , Células Cultivadas , Infecções por Coxsackievirus/imunologia , Enterovirus Humano B/efeitos dos fármacos , Indução Enzimática , Inibidores Enzimáticos/toxicidade , Imuno-Histoquímica , Isoenzimas/análise , Isoenzimas/biossíntese , Ativação de Macrófagos , Macrófagos/enzimologia , Macrófagos/imunologia , Camundongos , Camundongos Endogâmicos , Dados de Sequência Molecular , Miocardite/imunologia , Miocárdio/enzimologia , NG-Nitroarginina Metil Éster , Óxido Nítrico Sintase/análise , Óxido Nítrico Sintase/antagonistas & inibidores , Fragmentos de Peptídeos/síntese química , Fragmentos de Peptídeos/imunologia , Coelhos , Baço/enzimologia , Transcrição Gênica/efeitos dos fármacos , Replicação Viral/efeitos dos fármacos , ômega-N-MetilargininaRESUMO
This study examines the adjuvant properties of silicone oil, silicone gel and silicone elastomer using a foreign antigen, bovine serum albumin (BSA). Seventy male Harlan Sprague-Dawley rats, approximately 250 grams each, were divided into 7 groups: A- incomplete Freund's adjuvant (IFA) with BSA; B- silicone oil with BSA; C- IFA/silicone oil with BSA; D- 50% silicone gel/50% silicone oil with BSA; E- silicone oil/1000 microns elastomer particles with BSA; F- silicone oil/500 microns elastomer particles with BSA; G- saline with BSA. Rats were implanted intramuscularly with mixtures or emulsions of the above described treatment materials. Cardiac punctures were performed on days 0, 14, 28, 42, and 55. Serum IgG antibody response to BSA was determined by enzyme-linked immunosorbent assay (ELISA). Rats were sacrificed on day 55 and sections of the injection sites were collected and stained for histopathologic evaluation. The results demonstrated that silicone gel functions as a potent immunologic adjuvant as measured by a heightened IgG antibody response to BSA. In contrast silicone elastomer particles have no apparent adjuvant effect as determined by the low anti-BSA antibody levels in these treatment groups throughout the course of the study. Histologically, silicone gel and silicone elastomer elicit a moderate to severe "foreign body" granulomatous inflammatory response at the injection site. Silicone oil elicits mild or no local inflammatory response.
Assuntos
Adjuvantes Imunológicos/farmacologia , Elastômeros de Silicone/farmacologia , Silicones/farmacologia , Animais , Bovinos , Masculino , Ratos , Ratos Sprague-Dawley , Soroalbumina Bovina/imunologia , Óleos de Silicone/farmacologiaRESUMO
We have evaluated two recently published test procedures for demonstrating antibodies to silicone. Positive control serum samples provided to us by the original authors were positive in our hands, using the methods described. However, serum samples from patients with certain connective tissue diseases but no history of silicone implants were also positive. The question of silicone-specific antibodies remains unresolved.
