Cerebrospinal Fluid IL-6 Levels Research Articles

Helicobacter pylori Antigen in Stool Is Associated With SIDS and Sudden Infant Deaths due to Infectious Disease

Infection with Helicobacter pylori has been proposed to be a common cause of Sudden Infant Death Syndrome (SIDS). We investigated the frequency of H. pylori infection in 160 infant deaths and 156 live controls by means of the Helicobacter pylori stool antigen (HpSA) immunoassay. Histology was performed in 26 randomly selected cases. H. pylori antigen was detected in 8% (12/156) of the live controls compared with 25% (30/122) of SIDS cases (p < 0.001), 53% (9/17) of deaths due to infection (p < 0.001), and 9% (1/11) of accidental/violent deaths (p = 0.60). In the classic age peak for SIDS, 1-5 mo, 31% (21/67) of SIDS cases were HpSA positive compared with 1.5% (1/68) of live controls (p < 0.001). Rod-like immunoperoxidase positive H. pylori organisms were identified in 7/12 HpSA positive gastric antrum sections compared with 2/14 HpSA negative (p = 0.038). Significantly elevated IL-6 levels in cerebrospinal fluid representing signs of central immune stimulation were demonstrated in HpSA positive SIDS victims compared with HpSA negative victims (p = 0.045). Detection of H. pylori antigen in stool is associated with SIDS and deaths due to infections. We hypothesize that H. pylori infection in infancy may be involved as the triggering pathogen for sudden death during the first 5 month after birth.

Cerebrospinal fluid levels of cytokines in non-herpetic acute limbic encephalitis: Comparison with herpes simplex encephalitis

Background: Recently, non-herpetic acute limbic encephalitis (NHALE) was identified as a new subgroup of limbic encephalitis. The immunological pathophysiology of NHALE is still unclear. Methods: We measured the concentrations of interferon-γ (IFN-γ), tumor necrosis factor-α (TNF-α), interleukin-2 (IL-2), IL-4, IL-6, IL-10, and soluble TNF receptor 1 (sTNFR1) in the cerebrospinal fluid (CSF) of 15 patients with NHALE and 13 with herpes simplex encephalitis (HSE) by cytometric bead array or ELISA. Results: The CSF concentrations of IL-6 in patients with NHALE and IFN-γ, IL-6, IL-10, and sTNFR1 in HSE patients were significantly higher than those of controls ( p < 0.001, p = 0.004, p < 0.001, p = 0.018, and p < 0.001, respectively). There were significant correlations among CSF IL-6, IL-10, and sTNFR1 levels in HSE patients. The CSF concentrations of IFN-γ and sTNFR1 levels of patients with HSE were significantly higher than those with NHALE ( p = 0.001 and p = 0.002, respectively). Conclusions: CSF cytokine levels in NHALE were relatively low compared with those in HSE. These results may be related to the favorable prognosis of NHALE.

Effect of infliximab in progressive Neuro-Behçet's syndrome

Recent studies have shown the beneficial effect of infliximab in ocular manifestation of Behçet's disease. The current studies examined the efficacy of infliximab in progressive neuro-Behçet's syndrome (NB) refractory to methotrexate (MTX). Five male patients with progressive NB with sustained elevation of cerebrospinal fluid (CSF) IL-6 (over 20 pg/ml) despite administration of MTX and steroid, were given intravenous infusion of 5 mg/kg infliximab at weeks 0, 2, 6, and 14 with MTX (10-17.5 mg/week) and prednisolone (<10 mg/day) at the same doses. The clinical responses were judged by neuropsychiatric findings, revised Wechsler adult intelligence scale (WAIS-R), and brain magnetic resonance imaging (MRI) scans at 24 weeks. In all the 5 patients, CSF IL-6 were markedly decreased by 1/2-1/37 on the next day of the first infusion and remained below 20 pg/ml before the last infusion at 14 weeks, whereas CSF TNF-alpha were not significantly changed at any time point. At 24 weeks from the initial infusion, none of the 5 patients showed exacerbation (3 patients significantly improved). Nor did the atrophy in midbrain, pons and medulla on brain MRI scans show significant progression. These results suggest that infliximab might have a beneficial effect in the treatment of progressive NB by reducing CSF IL-6 levels but not TNF-alpha. Since infliximab has been shown to have cytotoxic effects on monocytes/macrophages, the rapid fall of CSF IL-6 after the infusion suggest that infliximab might directly act on such inflammatory cells producing IL-6.

IL-6 as a Biomarker of Ischemic Cerebrovascular Disease

The lack of a rapid and clinically accurate diagnostic tool remains a major obstacle to optimal care of patients with stroke. Cytokine changes in patients with acute stroke have been insufficiently studied. The purpose of this study is to delineate the relevance of IL-6 as a biochemical marker of stroke diagnosis, taking into account the genetic basis, and changes of the protein in serum and cerebrospinal fluid in relation to stroke development. Inflammation has an important role in ischemic cerebrovascular disease pathophysiology. Proinflammatory cytokines, such as IL-6, have been implicated in several mechanisms that might promote ischemic brain injury and an early neurological worsening. Cardiovascular diseases constitute one of the principal health problems in developing countries. Over the past few years, several studies have found evidence of the important role of inflammation in the ischemic cerebrovascular disease. The availability of a diagnostic biomarker panel for patients with stroke symptoms would be enormously valuable to complement clinical data and to precede radiological findings. IL-6 levels in cerebrospinal fluid and serum seem to reflect either the extent of tissue damage, or the accompanying clinical worsening. The -174 G/C functional polymorphism in the IL-6 gene might not be solely involved in disease susceptibility but also in linkage disequilibrium with other functional polymorphisms. Further studies are needed to solve this. Presently, the association between IL-6 genotype and stroke remains undetermined. Development of new neuroprotective therapies targeted to modulate cytokine-induced inflammation could be a promising way to prevent early deterioration in acute ischemic stroke.

A pediatric patient with neuro-Behçet’s disease

Behçet's disease is rare in childhood. We describe a 10-year-old boy with neuro-Behçet's disease (NB) who presented with fever, headache, vertigo, and hearing loss. An examination of the cerebrospinal fluid (CSF) revealed pleocytosis as well as elevated protein and interleukin (IL)-6 levels. Brain magnetic resonance imaging (MRI) showed hyperintensity of the right thalamus and midbrain on T2-WI, and gadolinium (Gd) enhancement of left acoustic nerve origin. HLA-B51 was positive. Prednisolone combined with methotrexate resulted in a complete remission. Brain MRI and the CSF IL-6 level were useful for the diagnosis and monitoring of this pediatric patient with NB.

Cerebrospinal fluid IL-6, HSP72, and TNF-α in exercising humans

During exercise the concentration of interleukin (IL)-6 and of heat shock protein (HSP) 72 increases in plasma, especially in fasting subjects. Both IL-6 and HSP72 are involved in a variety of metabolic and immunological processes, including some within the central nervous system and, accordingly, they are present not only in plasma but also in the cerebrospinal fluid (CSF). To evaluate whether, the two pools equilibrate we determined the levels of IL-6 and HSP72 in CSF, at a time when their plasma levels were increased due to exercise. Measurements of TNF-α served as a control, as its plasma level remains stable during exercise. Two groups of healthy, fit males performed 2 h of strenuous exercise with either carbohydrate ingestion ( n = 8) or placebo ( n = 8). The concentration of IL-6, HSP72, and TNF-α was measured in arterial blood and in the CSF obtained by a lumbar puncture immediately after exercise. A third group of subjects served as resting controls ( n = 8). At rest, CSF levels of IL-6 and HSP72 were 2- and 3-fold higher than the plasma levels, respectively ( P < .05). During exercise, with and without carbohydrate ingestion, plasma IL-6 increased 8- and 18-fold, respectively, and HSP72 increased 5-fold ( P < .05). However, the concentrations of IL-6 and HSP72 in CSF did not change with exercise and were therefore below their corresponding plasma levels. The concentration of TNF-α in CSF was below that in plasma and both remained stable during exercise. The findings that resting CSF levels of IL-6 and HSP72 are higher than in plasma and that they remain stable despite exercise-induced, profound increases in their systemic levels, suggest that the CSF pool is segregated from that in blood.

Analysis of serum and cerebrospinal fluid cytokine levels in subacute sclerosing panencephalitis in Papua New Guinea

Background Subacute sclerosing panencephalitis (SSPE) is a rare progressive inflammatory disease characterized by the persistent infection of the brain by the measles virus. However, the immunological pathophysiology of SSPE is still unclear. Methods We measured the concentrations of interferon-γ (IFN-γ), tumor necrosis factor-α (TNF-α), interleukin-2 (IL-2), IL-4, IL-6, IL-10, and soluble TNF receptor 1 (sTNFR1) in the serum and cerebrospinal fluid (CSF) of 23 patients with SSPE in Papua New Guinea (PNG), a country with a high incidence of SSPE, and Japanese controls by cytometric bead array or ELISA. Results The serum IL-6 and IL-10 levels of SSPE patients were significantly higher than those of controls ( p = 0.0075, and p = 0.0019, respectively). The serum IL-6 and IL-10 levels of SSPE patients with fever were significantly higher than those without fever ( p = 0.0107, and p = 0.0006, respectively). The CSF IL-6 levels of SSPE patients were significantly higher than those of controls ( p = 0.0218). The CSF IL-6 levels of SSPE patients with myoclonic jerks were significantly higher than those without myoclonic jerks ( p = 0.0189). There were no differences in serum IFN-γ, TNF-α, IL-2, IL-4, and sTNFR1, or CSF IFN-γ, TNF-α, IL-2, IL-4, IL-10, and sTNFR1 levels between the affected patients and controls. Conclusion Our present study suggests that serum IL-6 and IL-10 levels are related to fever, and the CSF IL-6 level, myoclonic jerks, in SSPE patients in PNG.

Cerebrospinal fluid tau, Aβ 1–42 and inflammatory cytokines in patients with Alzheimer's disease and vascular dementia

In this study we aimed to evaluate the possibility of using cerebrospinal fluid (CSF) tau, Aβ 1–42 and inflammatory cytokines for diagnosis of Alzheimer's disease (AD) and vascular dementia (VD). We measured levels of total tau (T-tau), phospho-tau (P-tau), Aβ 1–42, IL-6, and TNFα in CSF in groups of AD, VD, and controls using enzyme-linked immunosorbent assay (ELISA). T-tau level was found significantly higher in groups of AD ( t = 3.015, P < 0.01) and VD ( t = 2.872, P < 0.01) than in controls. IL-6 level as also higher in AD ( t = 2.883, P < 0.01) and VD ( t = 3.032, P < 0.01) than in controls. Both T-tau and IL-6 were not significantly different between AD and VD ( P > 0.05). The group of AD had remarkably higher P-tau ( t = 4.261 and 3.883, respectively, P < 0.01) and lower Aβ 1–42 ( t = 3.883 and 4.129, respectively, P < 0.01), as compared with those in VD and controls. TNFα level in AD was significantly higher than that in controls ( t = 2.745, P < 0.01), but lower than in VD ( t = 3.032, P < 0.01). Our data suggested that increment of T-tau and IL-6 levels in CSF was useful for screening AD and VD in certain population, while descending Aβ 1–42 and ascending TNFα in CSF are preferable to diagnose AD. In addition, a higher level of CSF P-tau might support AD diagnosis.

Acute disseminated encephalomyelitis in childhood: epidemiologic, clinical and laboratory features.

Acute disseminated encephalomyelitis (ADEM) is a central nervous system demyelinating disease that usually follows an apparently benign infection in otherwise healthy young persons. The epidemiology, infectious antecedents and pathogenesis of ADEM are poorly characterized, and some ADEM patients are subsequently diagnosed with multiple sclerosis (MS). We retrospectively (1991-1998) and prospectively (1998-2000) studied all persons aged < 20 years diagnosed with ADEM from the 3 principal pediatric hospitals in San Diego County, CA, during 1991-2000. Acute neurologic abnormalities and imaging evidence of demyelination were required for study inclusion. Epidemiologic variables, risk factors, clinical course, laboratory and radiographic findings, neuropathology and treatment data were analyzed. Interleukin (IL)-12, interferon-gamma (IFN-gamma) and IL-10 were assayed in blinded manner on cerebrospinal fluid (CSF) obtained prospectively from a subset of ADEM cases and compared with CSF from patients with enteroviral (EV) meningoencephalitis confirmed by polymerase chain reaction (PCR) and controls without pleocytosis. Data were analyzed on 42 children and adolescents diagnosed with ADEM during 1991-2000, and CSF IL-12, IFN-gamma and IL-10 levels were compared among ADEM (n = 14), EV meningoencephalitis (n = 14) and controls without pleocytosis (n = 28). Overall incidence of ADEM was 0.4/100,000/year; incidence quadrupled during 1998-2000 compared with earlier years. No gender, age stratum, ethnic group or geographic area was disproportionately affected. A total of 4 (9.5%) patients initially diagnosed with ADEM were subsequently diagnosed with MS after multiple episodes of demyelination. Although most children eventually recovered, 2 died, including 1 of the 3 ultimately diagnosed with MS. Magnetic resonance imaging was required for diagnosis among 74% of patients; computerized tomography findings were usually normal. Patients with EV had significantly higher mean CSF IFN-gamma (P = 0.005) and IL-10 (P = 0.05) than patients with ADEM and controls without CSF pleocytosis. CSF from ADEM patients had CSF cytokine values statistically similar to those of 3 patients subsequently diagnosed with MS. ADEM is a potentially severe demyelinating disorder likely to be increasingly diagnosed as more magnetic resonance imaging studies are performed on patients with acute encephalopathy. Further characterization of the central nervous system inflammatory response will be needed to understand ADEM pathogenesis, to improve diagnostic and treatment strategies and to distinguish ADEM from MS.

Cerebrospinal fluid interleukin (IL)-6 in unipolar major depression

Background: Previous studies have suggested that regulation of the proinflammatory cytokine interleukin (IL)-6 is abnormal in patients with major depression. This study was undertaken to determine whether IL-6 concentrations in cerebrospinal fluid (CSF) differ between depressed patients and healthy control subjects. Methods: Lumbar puncture with a standardized procedure was performed on 18 drug-free patients meeting DSM-IV criteria for unipolar major depression and 26 age- and sex-matched healthy volunteers. CSF was assayed for IL-6 using a quantitative ‘sandwich’ enzyme immunoassay technique. Results: Mean±S.D. CSF IL-6 levels did not differ between depressed (2.2±1.0 pg/ml) and healthy control (2.4±1.9 pg/ml) subjects. Limitations: This study had adequate power (0.8) to detect a large ( d=0.88) effect size at α=0.05. Although sample sizes were comparable to or larger than those of previous CSF studies, it is possible that a less robust difference between depressed and healthy subjects was not detected. Conclusions: These findings fail to support speculation that immune activation may be causally involved in the pathogenesis of depression.

Cerebrospinal fluid interleukin-6 in obsessive–compulsive disorder and trichotillomania

Recent studies have suggested that neuroimmune abnormalities may play an important role in the pathogenesis of obsessive–compulsive disorder (OCD) and related disorders. This study was undertaken to determine whether cerebrospinal fluid (CSF) concentrations of the proinflammatory cytokine interleukin (IL)-6 differ between OCD and trichotillomania patients and healthy control subjects. Lumbar puncture with a standardized procedure was performed on 26 patients with OCD and 9 with trichotillomania. All patients were drug-free and met DSM-IV criteria. Twenty-six age- and sex-matched healthy volunteers underwent the same procedure. CSF was assayed for IL-6 using a quantitative ‘sandwich’ enzyme immunoassay technique. Mean±S.D. CSF IL-6 levels did not differ between OCD patients ( n=26) (2.4±1.1 pg/ml) and controls ( n=26) (2.4±1.9 pg/ml) or between trichotillomania patients ( n=9) (2.3±0.8 pg/ml) and their matched controls ( n=14) (1.9±0.5 pg/ml). These findings fail to support speculation that ongoing immune activation may be causally involved in the pathogenesis of OCD or trichotillomania.

Effects of tacrolimus on hemispheric water content and cerebrospinal fluid levels of glutamate, hypoxanthine, interleukin-6, and tumor necrosis factor-α following controlled cortical impact injury in rats

Disturbance of calcium homeostasis contributes to evolving tissue damage and energetic impairment following traumatic brain injury (TBI). Calcium-mediated activation of calcineurin results in production of tissue-damaging nitric oxide and free oxygen radicals. Inhibition of calcineurin induced by the immunosuppressant tacrolimus (FK506) has been shown to reduce structural and functional damage after ischemia. The aims of the present study were to investigate time- and dose-dependent short-term antiedematous effects of tacrolimus following TBI. A left temporoparietal contusion (controlled cortical impact injury [CCII]) was induced in 51 male Sprague-Dawley rats. Tacrolimus (1 or 3 mg/kg body weight) was administered by a single intraperitoneal injection at 5 minutes, 30 minutes, or 4 hours after CCII occurred. Control rats received physiological saline. Water contents of traumatized and nontraumatized hemispheres, as well as cerebrospinal fluid (CSF) levels of mediators reflecting tissue damage (the proinflammatory cytokines interleukin [IL]-6 and tumor necrosis factor [TNF]-alpha, the excitotoxin glutamate, and the adenosine triphosphate-degradation product hypoxanthine), were determined 24 hours after trauma. Although CSF levels of IL-6 and TNFalpha were completely suppressed by tacrolimus at all time points and at both concentrations, CSF levels of glutamate and hypoxanthine, as well as edema formation, were only marginally influenced. Significant reduction of cerebral water content was confined to nontraumatized hemispheres. In addition, the higher dose of tacrolimus failed to exert significant antiedematous effects on traumatized hemispheres. Under the present study design, the potency of tacrolimus in reducing edema formation following CCII seems limited. However, its immunosuppressive effects could be of value in influencing the posttraumatic inflammatory response known to aggravate tissue damage.

Proinflammatory cytokines in cerebrospinal fluid in repair of thoracoabdominal aorta

Background. Little is known about alterations of cytokine levels in cerebrospinal fluid (CSF) during thoracoabdominal aortic surgery. We measured perioperative CSF cytokine levels to determine their clinical significances. Methods. Perioperative serum and CSF levels of cytokine were measured in 15 adult patients undergoing repair of the descending thoracic aorta (n = 4) or thoracoabdominal aorta (n = 11). All patients underwent prosthetic replacement and perioperative CSF drainage. Serum and CSF levels of tumor necrosis factor-α, Interleukin- (IL-) 1β, IL-6, IL-8, IL-10, and IL-12 were measured before operation and at 0, 6, 12, 18, 24, 48, and 72 hours postoperatively using enzyme-linked immunosorbent assays. Results. There were no hospital deaths, but 1 patient suffered paraplegia. Cerebrospinal fluid IL-8 levels peaked at immediately after operation (751.7 ± 42.1 pg/mL versus preoperative levels, 54.9 ± 24.6 pg/mL; p < 0.001), and the higher levels persisted for 72 hours. In contrast, serum IL-8 levels did not change and remained lower than CSF levels. The patient with paraplegia had the highest CSF IL-8 levels throughout the study period. Serum and CSF levels of tumor necrosis factor-α, IL-1β, IL-6, and IL-12 did not significantly change. Serum and CSF levels of IL-10 were significantly elevated after operation compared with preoperative levels. In contrast to IL-8, serum IL-10 levels surpassed CSF levels. Conclusions. Cerebrospinal fluid IL-8 levels are significantly elevated in thoracoabdominal aortic operation, and may be the most sensitive to the inflammatory response in the ischemic spinal cord injury. Persistent elevation of CSF IL-8 levels may be predictive of further development of neurologic deficits, and a reduction of proinflammatory cytokine levels may be a beneficial effect of CSF drainage, but this requires further investigation.

Immune mediators in cerebrospinal fluid during cryptococcosis are influenced by meningeal involvement and human immunodeficiency virus serostatus.

Pro- and anti-inflammatory mediators (tumor necrosis factor [TNF]-alpha, interleukin [IL]-6, IL-8, IL-10, and soluble TNF receptor II [sTNFR] II) were measured in cerebrospinal fluid (CSF) before treatment (day 0), and after 2 weeks and 3 months of antifungal therapy in 51 human immunodeficiency virus (HIV)-positive and 7 HIV-negative patients with culture-confirmed cryptococcosis. On day 0, all mediator concentrations, except IL-10 in HIV-positive patients, were higher in patients with meningeal, rather than extrameningeal cryptococcosis or in control subjects (P<.05). For meningitis patients, all mediator levels, except sTNFR II, were higher in HIV-negative than HIV-positive patients (P<.05). Day 0 CSF IL-8 levels were higher in HIV-positive patients receiving antiretroviral therapy than in untreated persons (P<.02). Day 0 sTNFR II levels were higher in HIV-positive survivors at 3 months, and elevated levels were sustained in HIV-positive patients with meningitis. Overall, these data support the idea that inflammatory responses are crucial to the eradication of cryptococcal infections in the central nervous system.

Temporal profile of cerebrospinal fluid glutamate, interleukin-6, and tumor necrosis factor-α in relation to brain edema and contusion following controlled cortical impact injury in rats

Traumatic brain injury is associated with release of the excitotoxin glutamate and production of pro-inflammatory cytokines IL-6 and tumor necrosis factor-α (TNF-α). Following controlled cortical impact injury, cerebrospinal fluid (CSF) glutamate, IL-6, and TNF-α concentrations were measured to investigate their relationship to evolving tissue damage. Compared to non-traumatized rats CSF glutamate, IL-6 and TNF-α levels were significantly increased by 8 h after trauma ( P<0.005). Parallel to increasing brain swelling and contusion CSF glutamate was significantly elevated over time, reaching highest levels by 48 h (33±4 μM) while IL-6 and TNF-α showed maximum values at 24 h after trauma (42±7 and 4.7±1 pg/ml) ( P<0.005). The observed different temporal profile of CSF glutamate, IL-6, and TNF-α following focal traumatic brain injury could be of therapeutic importance.

Inhibition of leukocyte entry into the brain by the selectin blocker fucoidin decreases interleukin-1 (IL-1) levels but increases IL-8 levels in cerebrospinal fluid during experimental pneumococcal meningitis in rabbits.

The polysaccharide fucoidin is a selectin blocker that inhibits leukocyte recruitment into the cerebrospinal fluid (CSF) during experimental pneumococcal meningitis. In the present study, the effect of fucoidin treatment on the release of the proinflammatory cytokines tumor necrosis factor alpha (TNF-alpha), interleukin-1 (IL-1), and IL-8 into the CSF was investigated. Rabbits (n = 7) were treated intravenously with 10 mg of fucoidin/kg of body weight every second hour starting 4 h after intracisternal inoculation of approximately 10(6) CFU of Streptococcus pneumoniae type 3 (untreated control group, n = 7). CSF samples were obtained every second hour during a 16-h study period. Treatment with fucoidin caused a consistent and significant decrease in CSF IL-1 levels (in picograms per milliliter) between 12 and 16 h (0 versus 170, 0 versus 526, and 60 versus 1,467, respectively; P < 0.02). A less consistent decrease in CSF TNF-alpha levels was observed in the fucoidin-treated group, but with no significant difference between the two groups (P > 0.05). In contrast, there was no attenuation in CSF IL-8 levels. Indeed, there was a significant increase in CSF IL-8 levels (in picograms per milliliter) in the fucoidin-treated group at 10 and 12 h (921 versus 574 and 1,397 versus 569, respectively; P < 0.09). In conclusion, our results suggest that blood-derived leukocytes mainly are responsible for the release of IL-1 and to some degree TNF-alpha into the CSF during pneumococcal meningitis, whereas IL-8 may be produced by local cells within the brain.

IL-6 Cerebrospinal Fluid Levels Are Related to Laryngeal IgA and Epithelial HLA-DR Response in Sudden Infant Death Syndrome

The objective was to investigate whether there is any correlation between signs of central and peripheral immune stimulation in victims of sudden infant death syndrome (SIDS), the former expressed by IL-6 in cerebrospinal fluid (CSF), the latter by IgA, IgG, and IgM immunocytes, T lymphocytes, and HLA-DR expression in laryngeal mucosa. Seventeen SIDS cases with low CSF IL-6 levels (< or =5 pg/mL) and 20 cases with high CSF IL-6 levels (> or =30 pg/mL) were subjected to immunohistochemical quantitation of IgA, IgG, and IgM immunocytes; semiquantitative scoring of T lymphocytes in the mucosa of epiglottis and larynx, and semiquantitative evaluation of HLA-DR expression. SIDS cases with IL-6 levels > or =30 pg/mL had a significantly higher number of IgA immunocytes in laryngeal mucosa (p = 0.007) and in epiglottis (p = 0.03) than cases with IL-6 levels < or =5 pg/mL. Furthermore, laryngeal HLA-DR expression was significantly more extensive in SIDS cases with IL-6 levels > or =30 pg/mL than in those with levels < or =5 pg/mL (p = 0.05). No differences were found for IgG and IgM immunocytes or for T cells. In addition, babies found prone more often had symptoms of slight infection before death and had a higher number of IgA immunocytes in the larynx (p = 0.02) than babies sleeping on their side or back. Because IL-6 levels > or =30 pg/mL correspond to the levels found in infants who die from infectious diseases such as meningitis/septicemia and pneumonia, the findings favor the hypothesis that many SIDS cases may be caused by an "overreaction" of the immune system to an otherwise harmless infection.

Are elevated cerebrospinal fluid levels of IL-6 in sudden unexplained deaths, infectious deaths and deaths due to heart/lung disease in infants and children due to hypoxia?

Many SIDS cases probably die after periods of hypoxia and it has been shown that hypoxia may stimulate IL-6 production. The purpose of this paper was to examine if there were any correlations between hypoxanthine in vitreous humour and IL-6 in CSF. The concentration of IL-6, IL-1beta and TNFalpha in cerebrospinal fluid of 50 Sudden Infant Death syndrome (SIDS) cases, 9 borderline SIDS cases, 18 infectious deaths, 8 violent deaths and 22 cases with heart/lung disease were measured by ELISA. The hypoxanthine (Hx) vitreous humour concentrations in the same groups were determined by high performance liquid chromatography. The IL-6 levels in cases of infectious death, heart/lung disease and borderline cases were significantly higher than in the SIDS cases (p < 0.01). The Hx levels were in the same range in cases of SIDS, borderline SIDS and infectious death, and they were significantly higher than the levels in cases of violent death and heart/lung disease (p < 0.01). There was no correlation between hypoxanthine and IL-6 in any of the groups. In the cases studied IL-6 elevation is probably not induced by hypoxia, but is rather a result of immunological stimulation.

Interferon-gamma potentiates interleukin (IL)-6 and tumor necrosis factor-alpha but not IL-1beta induced by endotoxin in the brain.

Because interferon-gamma (IFN gamma) is present in the central nervous system during neurologic diseases associated with inflammation, its effect on endotoxin-induced cytokines was studied. Cerebrospinal fluid (CSF) and serum levels of interleukin (IL)-1beta, IL-6, and tumor necrosis factor-alpha (TNF alpha), their messenger RNA expression in brain areas (hypothalamus, hippocampus, and striatum) and in spleen were evaluated 2 and 8 h after endotoxin [lipopolysaccharide (LPS), 25 microg/rat i.c.v.], IFN gamma (2.5 microg/rat i.c.v.) or after their coadministration in rats. CSF and serum IL-1beta levels were increased by LPS alone and IFN gamma coadministration did not furtherly increase them. IFN gamma potentiated LPS effect on IL-6 and TNF alpha levels in both CSF and serum. LPS and IFN-gamma coadministration did not alter IL-1beta messenger RNA expression induced by LPS in brain areas and in spleen, but it potentiated that of IL-6 and TNF alpha. The present in vivo data show that i.c.v. coadministration of LPS and IFN gamma results in a potentiation of cytokine production (IL-6 and TNF alpha) which may trigger a cascade of events relevant to neurodegenerative processes. This action is independent of IL-1beta because the production of this cytokine is not altered by IFN gamma treatment.

Evaluation of IL-2, sIL2R, IL-6, TNF-α, and IL-1β levels in serum and CSF of patients with optic neuritis

Optic neuritis (ON) is characterized by immune-mediated demyelination of the optic nerve. In this study we addressed the question of cytokine signalling as part of activation of the immune system. 20 patients with first episode of acute idiopathic unilateral ON, prolonged visual evoked potentials, but normal 1.5 tesla MRI of the brain, and normal somatosensory evoked potentials were included into the study. Paired cerebrospinal fluid (CSF) and serum samples of these patients were analyzed for the presence of interleukin (IL-)-2, soluble IL-2R (sIL2R), IL-6, tumor necrosis factor (TNF)-α, and IL-1β by an enzyme-linked immunosorbent assay (IL-2, sIL2R, TNF-α, IL-1β) or a bioassay (IL-6). IL-2 was significantly elevated in the CSF ( P < 0.01), whereas sIL2R ( P < 0.01) and IL-6 ( P < 0.01) were significantly increased in serum. TNF-α could not be detected in CSF or serum, and IL-1β was negative in serum in all but one sample and positive in only low amount (mean 9 pg/ml) in the CSF of 6 20 patients. This cytokine pattern in ON indicates an activation of the immune system within and outside the central nervous system with a predominance of T-cell activation.