Serum and cerebrospinal fluid nitrite/nitrate levels in patients with rotavirus gastroenteritis induced convulsion

Kawashima, Hisashi; Inage, Yukiko; Ogihara, Masahiko; Kashiwagi, Yasuyo; Takekuma, Kouji; Hoshika, Akinori; Mōri, Takayuki; Watanabe, Yasuo

doi:10.1016/j.lfs.2003.08.014

Cited by 72 publications

(48 citation statements)

References 22 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…More recent evidence generated in studies with rotavirus-infected children suggests that IL-6 is one of the cytokines positively correlated with recovery time (13,31). Interestingly, it has been suggested that in patients with possible rotavirus-induced encephalopathy, IL-6 may positively correlate with levels of nitric oxide in serum and cerebrospinal fluid and with convulsive seizures (15). In our study, IL-6 secretion was detected from both CD4 ϩ and CD8 ϩ T lymphocyte subsets obtained from the peripheral blood of juvenile rhesus macaques with a history of rotavirus infection.…”

Section: Discussionsupporting

confidence: 47%

See 1 more Smart Citation

Defining T-Cell-Mediated Immune Responses in Rotavirus-Infected Juvenile Rhesus Macaques

Sestak

McNeal

Choi

et al. 2004

J Virol

View full text Add to dashboard Cite

The appearance of virus-specific CD4؉ and/or CD8 ؉ T lymphocytes in peripheral blood of captive juvenile rhesus macaques (Macaca mulatta) was observed following rotavirus infection. These cell-mediated immune responses were measured following experimental or natural infection after rotavirus was isolated from stool specimens of asymptomatic animals. The virus isolated was a new strain of simian rotavirus that we named TUCH (for Tulane University and Cincinnati Children's Hospital). Restimulation of peripheral T lymphocytes by inactivated double-or triple-layered TUCH rotavirus particles containing either VP6 or VP4 and VP7 on their respective surfaces resulted in increased quantities of interleukin-6 (IL-6) and IL-12 in cell culture supernatants. Recall responses to rotavirus by CD4 ؉ and CD8 ؉ T lymphocytes were associated with accumulation of intracellular IL-6 and gamma interferon. Antigen presentation of TUCH rotavirus to lymphocytes was mediated via differentiated cultures of monocyte-derived dendritic (HLA-DR ؉ ) cells. This is the first report demonstrating cell-mediated immune responses to rotavirus in nonhuman primates. Further exploration of rhesus macaques in vaccine trials with human rotavirus vaccine candidates is the major objective of future studies.In the United States, rotavirus infection of 6-to 36-monthold children results in more than 50,000 hospitalizations each year (41). Throughout the world, at least 500,000 children die annually due to rotavirus-induced dehydration (25,28,41). Although extensive trials of novel vaccine candidates were performed with gnotobiotic piglets or genetically defined mice (28,41,44), none of these candidates have been evaluated in primates. Therefore, development of a nonhuman primate (NHP) model for evaluation of human rotavirus vaccine candidates is urgently needed. Although several NHP species, including chimpanzees and baboons as well as rhesus, vervet, pigtailed, and squirrel monkeys, have been reported to seroconvert to rotavirus with high, virus-specific antibody titers, no studies on cell-mediated immune responses have been conducted with an NHP model in the context of rotavirus (11,14,29,36,43). One reason is that clinical disease associated with rotavirus infection in NHPs, which has been reported to be limited to the first days or weeks of life (20,21,29,36,42), is difficult to produce experimentally.In this study, the cell-mediated immunological responses to rotavirus infection in juvenile rhesus macaques that were housed in biosafety level 2 facilities of the Tulane National Primate Research Center (TNPRC) were evaluated. We anticipated that cell-mediated immune responses could be measured in these animals by the time passive maternally acquired immunity subsided, i.e., at between 4 and 6 months of age. Thus, we studied the T lymphocytes collected from peripheral blood of juvenile rhesus macaques after a detectable rotavirus infection. Based on recent studies with the adult mouse model (4, 5, 24), our hypothesis was that immunological memory in rotav...

show abstract

Section: Discussionsupporting

confidence: 47%

“…Cytokines measured in cell culture supernatants or through intracellular (34,39,40). Previously, elevated levels of both IL-6 and IFN-␥ were reported in studies with rotavirus-infected human patients (12,13,15,31). In a study with IL-6-deficient mice, it was found that both IL-6…”

Section: Discussionmentioning

confidence: 99%

Defining T-Cell-Mediated Immune Responses in Rotavirus-Infected Juvenile Rhesus Macaques

Sestak

McNeal

Choi

et al. 2004

J Virol

View full text Add to dashboard Cite

show abstract

“…This suggests that the level of rotavirus antigen in CSF is less than that in the serum. Consequently, we suggest that the main pathogenesis of neurological complications in severe rotavirus infection results from indirect mechanisms, such as diffuse endothelialitis (Morrison et al, 2001), cytokine storm (Ioi et al, 2006), and nitrogen oxides (Kawashima et al, 2004), and not through the direct invasion of rotavirus into the central nervous system.…”

Section: P<005mentioning

confidence: 88%

Pathophysiological analysis of five severe cases with rotavirus infection

et al. 2015

View full text Add to dashboard Cite

Introduction: Rotavirus infection is usually localized to the intestine. Severe cases with extraintestinal symptoms are rare, and its pathogenesis remains unclear.Case presentation: We report severe rotavirus infections in five previously healthy, unvaccinated children that occurred in the 2011 season in Aichi Prefecture, Japan. All cases had short histories of recurrent diarrhoea and vomiting that preceded extraintestinal symptoms. Two cases with prolonged seizures and unconsciousness were diagnosed with encephalitis/encephalopathy; one case died and the other survived with severe neurological sequelae in spite of intensive treatment including anticytokine therapy. Another two cases had rapidly worsening cardiopulmonary dysfunction and seizures, and they died a few hours after admission despite cardiopulmonary support. The last case was transferred to hospital in cardiopulmonary arrest and resuscitation was unsuccessful. All cases had positive stool samples for rotavirus RNA, and the rotavirus antigen was also detected in the serum of four cases, but not in the cerebrospinal fluid (CSF). Serum IL-6 and IL-10 levels were significantly higher in the severe cases than in children with rotavirus gastroenteritis without extraintestinal symptoms, and serum IL-10 levels were significantly higher than CSF levels in the severe cases.Conclusion: Cytokines appear to mediate the pathogenesis of severe rotavirus infection with extraintestinal involvement. In conclusion, these cases highlight the need for a routine rotavirus immunization programme.

show abstract

“…On this background, a recent finding from the USA is remarkable; a full course of rotavirus vaccination was statistically associated with an 18-21% reduction in risk of seizure requiring hospitalization or emergency department care in the year following vaccination, compared with unvaccinated children. This demonstrates that rotavirus immunization not only directly prevents systemic rotavirus infection, including extra-intestinal complications involving the central nervous system, 3 but also prevents secondary effects of rotavirus infection such as rotavirusrelated elevation of nitric oxide in cerebrospinal fluid inducing neurotoxicity, 4,16 and/or calcium channel fluctuations resulting in neurotransmitter dysregulation. 15 This reduction in childhood seizures complements the well-documented vaccine related benefit of a reduction in the number of patients hospitalized in the US due to diarrhea caused by rota-virus.…”

Section: The Role Of Rotavirus Immunization Beyond Infant Acute Gastrmentioning

confidence: 89%

Mucosal Immunity and acute viral gastroenteritis

Rose

2014

Human Vaccines & Immunotherapeutics

View full text Add to dashboard Cite

Serum and cerebrospinal fluid nitrite/nitrate levels in patients with rotavirus gastroenteritis induced convulsion

Cited by 72 publications

References 22 publications

Defining T-Cell-Mediated Immune Responses in Rotavirus-Infected Juvenile Rhesus Macaques

Defining T-Cell-Mediated Immune Responses in Rotavirus-Infected Juvenile Rhesus Macaques

Pathophysiological analysis of five severe cases with rotavirus infection

Mucosal Immunity and acute viral gastroenteritis

Contact Info

Product

Resources

About