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The pathology of Q fever hepatitis. A case diagnosed by liver biopsy.

A 52-year-old woman with fever and low grade hepatitis had Q fever, a diagnosis made by the characteristic granulomas, containing fibrin and vacuoles, on liver biopsy and confirmed by serology. Fibrin was demonstrated in the granulomas but Coxiella burnetii antigens were not. The literature on the histopathology of the liver in both acute Q fever and Q fever endocarditis shows that none of the 220 cases of Q fever endocarditis, with one possible exception, had the characteristic granulomas of acute Q fever. Rather they displayed a range from normality through nonspecific reactive hepatitis to occasional nonspecific granulomas. Thus, the characteristic granulomas of acute Q fever appear to be transient even if active infection persists. The definition of chronic Q fever should have a temporal characteristic rather than a serologic one.

Female↗

Fever and infectious complications after percutaneous acetic acid injection therapy for hepatocellular carcinoma: incidence and risk factor analysis.

BACKGROUND: Ultrasound-guided percutaneous acetic acid injection (PAI) therapy is effective for hepatocellular carcinoma (HCC). Posttreatment fever (>37.5 degrees C) may occur owing to acetic acid-induced tumor necrosis, but its incidence and clinical significance are not clear. METHODS: A total of 402 treatment sessions in 127 consecutive patients undergoing PAI for HCC were prospectively studied. The incidence and risk factors associated with post-PAI fever were analyzed. RESULTS: There were 37 (9.2%) episodes of fever occurring in 29 HCC patients after PAI. Patients who developed fever more often had large-sized (3.5+/-1.3 cm vs. 2.7+/-1.2 cm, P=0.0002) tumor and a higher injection volume (2.6+/-0.1 mL vs. 2.2+/-0.1 mL, P=0.001) of acetic acid compared with those without fever. Multivariate logistic regression analysis showed that tumor size >3 cm was the only significant predictor associated with occurrence of posttreatment fever (odds ratio: 4.4, 95% confidence interval: 2.2-8.9, P<0.001). Three patients, all of whom had HCC diameter >3 cm, had 4 episodes of bacteremia after treatment; one of them developed liver abscess that required percutaneous drainage. CONCLUSIONS: Fever after PAI is not an uncommon event. Patients with tumor size >3 cm have a higher risk of posttreatment fever. Bacteremia and significant infectious complication could occur in a minority of patients. Prophylactic antibiotics before treatment may be necessary for high-risk patients.

Abscess↗

Fever following intracavitary bacillus Calmette-Guerin therapy for upper tract transitional cell carcinoma.

PURPOSE: We attempted to identify the source of fever during intracavitary upper tract instillation of bacillus Calmette-Guerin (BCG). MATERIALS AND METHODS: Of 34 patients who had previously undergone percutaneous resection of upper tract transitional cell carcinoma 18 received weekly intracavitary BCG through the nephrostomy tubes for 6 consecutive weeks. After treatment 6 all patients underwent nephroscopy and biopsy, and all cases were retrospectively reviewed. Parameters analyzed were BCG related symptoms, maximum temperature during treatment, maximum renal pelvic pressure during treatment, culture results, chest x-ray findings, pretreatment serum creatinine concentration, serum liver enzyme values, untoward events and treatments performed for BCG related complications. RESULTS: No obvious pattern in appearance of fever occurred. During 88 treatment episodes evaluated there were 14 temperature elevations to more than 100F in 7 patients (39%). Positive urine cultures were associated with fever in only 4 cases and none was positive for Mycobacterium. There was no correlation between greater renal pelvic pressures and fever. All chest radiographs and serum creatinine levels were unchanged, and liver enzymes were normal in all but 1 patient. Two patients had prolonged fever with elevations to greater than 104F following treatment: 1 died in a motor vehicle accident and 1 died after the third BCG infusion led to overwhelming sepsis. No source of fever was identified in either patient. CONCLUSIONS: Patients with low grade fever coincident with upper tract BCG may be treated conservatively simply by withholding the infusion. Fever greater than 103F should be considered an emergency condition with high potential for mortality. Immediate and aggressive attempts at identifying a source along with institution of antituberculous therapy are priorities.

Adjuvants, Immunologic↗

Fever during treatment for bacterial meningitis.

The records of 476 infants and children with bacterial meningitis treated between 1979 and 1982 were reviewed. By the sixth hospital day 90% or more of children with pneumococcal or meningococcal infection compared with 72% of children with Haemophilus infection (P less than 0.001) were afebrile. The rates of prolonged fever for 10 days or more, persistent fever for 5 to 9 days and secondary fever were 13, 13 and 16%, respectively. The conditions associated with prolonged fever for 10 days or more were subdural effusion (27%), drug fever (23%) and concomitant arthritis or pneumonia (20%); 15% were of indeterminable cause. The principal conditions associated with persistent fever for 5 to 9 days were other foci of disease (17%), nosocomial infections (16%) and subdural effusion (14%); in 42% the cause was unknown. The conditions associated with secondary fever were nosocomial infections (27%) and subdural effusion (23%); 39% were of indeterminable cause. Neither the duration nor the patterns of fever correlated with neurologic abnormalities at discharge, including hearing deficit.

Child↗

Duration of fever and its relationship to bacteremia in febrile outpatients three to 36 months old. The Occult Bacteremia Study Group.

OBJECTIVE: To determine the relationship between the duration of fever as reported by caregivers and the likelihood of occult bacteremia in highly febrile young children. METHODS: This is a prospective cohort study performed as part of a prior, multicenter, randomized, interventional trial of oral versus intramuscular antibiotics in the prevention of complications of occult bacteremia in febrile children presenting to nine urban pediatric emergency departments at eight medical centers. Participants included children three to 36 months of age with a temperature of > or = 39.0 degrees C and a nonfocal illness (or uncomplicated otitis media) managed as outpatients. The outcome measure was the presence of bacteremia. RESULTS: Of the 6680 randomized patients, 6619 (99.1%) had a culture of their blood and a valid reported duration of fever. The median duration of fever in patients with bacteremia (n = 192) and without bacteremia (n = 6427) was the same, one to two days, but the mean rank of patients with bacteremia was significantly lower than that of patients without bacteremia (P + 0.0009). A significantly greater proportion of patients with fever < 1 day had bacteremia than patients with fever > or = 1 day (P = 0.004), and a significantly greater proportion of patients with fever < 2 days had bacteremia than patients with fever > or = 2 days (P = 0.009). The sensitivity, specificity, positive predictive value, and negative predictive value of fever < 1 day in detecting occult bacteremia were 40.1, 69.8, 3.8, and 97.5%, respectively.

Anti-Bacterial Agents↗

Predicting bacteremia in children with fever and chemotherapy-induced neutropenia.

BACKGROUND: Fever and neutropenia are common clinical problems in pediatric oncology and frequently necessitate emergency hospitalization and immediate empiric broad spectrum antimicrobial therapy. Estimating the risk of bacteremia in fever and neutropenia is a challenge. The purpose of this study was to develop an algorithm predicting the risk of bacteremia and Gram-negative bacteremia in children and adolescents with fever and neutropenia, based on information accessible at presentation. METHODS: We collected information available within 2 h of presentation of children with fever and neutropenia and, on outcome, from all pediatric cancer patients presenting with fever and neutropenia from 1993 through 2001 in a retrospective single center cohort study. After univariate analyses a multivariate decision tree was constructed, and its performance was evaluated by cross-validation. RESULTS: Bacteremia was detected in 87 (24%) and Gram-negative bacteremia in 30 (8%) of 364 episodes of fever and neutropenia. At the predetermined sensitivity level, > or =95%, decision tree models reached cross-validated specificities of 37 and 43%, with negative predictive values of 96 and 99%, for bacteremia and Gram-negative bacteremia, respectively. Absence of a clinically or radiologically evident source of infection and previous episodes of fever and neutropenia were defined as two newly described factors associated with bacteremia. CONCLUSIONS: Based on this retrospective analysis, it appears that bacteremia can be predicted with clinically useful specificity at a high level of sensitivity, using clinical information available at presentation in pediatric cancer patients with fever and neutropenia.

Adolescent↗

Fever and haemolysis in Hodgkin's diseases.

One hundred and four patients with Hodgkin's disease have been studied retrospectively in order to evaluate the relationship between fever associated with the disease (Pel-Ebstein type) and the development of anaemia. In the material 19 episodes of fever were found to be of this type. The mean loss of Hb during a fever period was 14% (range 2-33). From the rate of decrease in Hb it was deduced that this was at least partly caused by an increased destruction of erythrocytes. There was a significant correlation between the thermal exposure (expressed either as the duration of fever, the maximum body temperature during the fever period, or the sum of the temperature maxima) and the degree of erythrocyte loss. The loss of Hb was self-limited in spite of persistent fever. Furthermore, there seemed to be an inverse relationship between the degree of preexisting anaemia and the fever-induced relative loss of Hb. A possible explanation is that the older part of the erythrocyte population is more sensitive to the effect of fever.

Erythrocytes↗

Fever management: paediatric nurses' knowledge, attitudes and influencing factors.

AIMS: This paper describes Australian paediatric nurses' knowledge of and attitudes toward fever and its management and the predictors of their intentions to administer paracetamol to a febrile child. BACKGROUND: Despite evidence-based support for the beneficial effects of fever over the past three decades, health professionals' negative attitudes toward fever and their reliance on antipyretics to reduce it have persisted and continue to be reported in the literature. METHODS: A self-report questionnaire was used. An instrument was developed, piloted by test-retest and revised prior to data collection. Fifty-one paediatric nurses working in medical wards of a metropolitan paediatric hospital in Australia participated. RESULTS: Nurses' mean knowledge score about the physiology of fever, general fever management and antipyretics was 62%, which was not as high as expected. Participants reported positive attitudes toward the benefits of fever, the necessity for its reduction in children with pre-existing cardiac or respiratory conditions and towards regular antipyretic administration masking the infective process. Negative attitudes included disbelief that temperature is often unrelated to illness severity. Conflicting attitudes toward febrile convulsions were highlighted by beliefs that antipyretic therapy prevents these and that antipyretics do not prevent initial febrile convulsions. Predictors of intentions to administer paracetamol were beliefs about the effectiveness of paracetamol and nurses' beliefs about the expectations of others in relation to paracetamol administration. Nurses reported strong intentions to administer paracetamol to the next febrile child they cared for. Limitations of the study include the use of a nurse manager for recruitment and collecting the data at only one site. CONCLUSIONS: Fever management is an integral aspect of paediatric nursing. For its consistent rational management, nurses must have appropriate knowledge and positive attitudes. This highlights the need for continuing education in fever management.

Acetaminophen↗

Resolving diagnostic uncertainty in initially poorly localizable fevers: a prospective study.

AIMS: Prospective, observational data collection of fever patients with regard to aetiology and means of detecting it particularly noting the factors, which quickly helped resolve diagnostic uncertainty. METHODS: Prospective follow-up of patients with clinically non-localizable fever admitted to Manipal Teaching Hospital, Pokhara, Nepal, documenting their temperature response, clinical and lab findings and diagnoses with their response to treatment. RESULTS: Enteric fever 56.8% (25), urinary tract infection 15.9% (7), malaria 9% (4), TB (pulmonary) 4% (2), abscess 4% (2) and hydatid cyst 4% (2). Remaining 4% were due to some other systemic causes. Culture positive: Salmonella typhi positive 32% (8), S. paratyphi positive 20% (5) and culture negative 48%. Response to treatment: enteric fever--(i) first-line drugs (ampicillin/cotrimoxazole) 16% (4), (ii) second-line drugs (ciprofloxacin) 20% (5) and (iii) ceftriaxone 44% (11). CONCLUSIONS: Fever charting as a means to localize Salmonella vs other fevers is still an invaluable clinical tool in adult patients in Nepal. If used judiciously, it can be used as an effective means to diagnose and treat patients of initially non-localizable fevers. Patience must be exercised in starting antibiotics, not until the fever pattern of 2 days suggests enteric, and also while waiting for a response to first-line drugs for Salmonella before one switches over to costlier second-line drugs, with the possible exception of quinolones which may even be used first line owing to their reduced costs (at the danger of wielding a double-edged sword).

Adolescent↗

Maternal fever in term labour in relation to fetal tachycardia, cord artery acidaemia and neonatal infection.

OBJECTIVE: To determine 1. whether maternal fever during term labour is associated with acidaemia at birth and neonatal infection and 2. whether fetal tachycardia precedes maternal fever and is associated with neonatal infection. DESIGN: Retrospective matched-pair case-control study. SUBJECTS: Two hundred and forty-eight newborn infants whose mothers developed fever during term labour (cases) and 248 control infants. The women were matched for parity and duration of labour. MAIN OUTCOME MEASURES: Cord artery acid-base status, Apgar scores, neonatal infections, and fetal heart rate before maternal fever. RESULTS: Mean pH, as well as the rate of cord artery acidaemia at birth (pH < 7.10) was equal in cases and controls (in both groups 7.24% and 6%, respectively). Signs of septicaemia and/or pneumonia were identified in 17 case newborns (7%) and in one control (0.4%; OR 17.0, P < 0.001). Of 212 pairs with complete heart rate data, fetal tachycardia preceded maternal fever in 39 cases (18%) and in 16 controls (8%) (OR 2.6, P = 0.003). Tachycardia before maternal fever was not associated with increased neonatal infectious morbidity. CONCLUSIONS: Maternal fever during term labour was associated with perinatal infection, but not with acidaemia at birth. Elevated fetal heart rate preceded maternal fever in a minority of cases and was not associated with perinatal infection.

Acidosis↗

Brief report: incidence, etiology, risk factors, and outcome of hospital-acquired fever: a systematic, evidence-based review.

OBJECTIVES: Temperature is universally measured in the hospitalized patient, but the literature on hospital-acquired fever has not been systematically reviewed. This systematic review is intended to provide clinicians with an overview of the incidence, etiology, and outcome of hospital-acquired fever. DATA SOURCES: We searched MEDLINE (1970 to 2005), EMBASE (1988 to 2004), and Web of Knowledge. References of all included articles were reviewed. Articles that focused on children, fever in the developing world, classic fever of unknown origin, or specialized patient populations were excluded. REVIEW METHODS: Articles were reviewed independently by 2 authors before inclusion; a third author acted as arbiter. RESULTS: Of over 1,000 studies reviewed, 7 met the criteria for inclusion. The incidence of hospital-acquired fever ranged from 2% to 17%. The etiology of fever was infection in 37% to 74%. Rates of antibiotic use for patients with a noninfectious cause of fever ranged from 29% to 55% for a mean duration of 6.6 to 9.6 days. Studies varied widely in their methodology and the patient population studied. CONCLUSIONS: Limited information is available to guide an evidence-based approach to hospital-acquired fever. We propose criteria to help standardize future studies of this important clinical situation.

Cohort Studies↗

Seizures with fever after unprovoked seizures: an analysis in children followed from the time of a first febrile seizure.

PURPOSE: To determine how the onset of unprovoked seizures influences recurrence of seizures with fever in children followed from the time of a first febrile seizure. METHODS: In a prospective cohort of children (n = 428) identified at the time of a first febrile seizure, predictors of a second seizure with fever were identified. The occurrence of a first unprovoked seizure was treated as a time-dependent covariate in a Cox regression model rather than as a censoring point as it traditionally has been in the past. RESULTS: One hundred forty-three (33.4%) children had further seizures. Seven had further seizures with fever only after onset of unprovoked seizures. After adjustment was made for the four previously described predictors of recurrent febrile seizures (age at onset, family history, height of fever, and duration of fever), the onset of unprovoked seizures was associated with a rate ratio of 3.47 (p = 0.0015), indicating a large increase in the risk of further seizures with fever after onset of unprovoked seizures. CONCLUSIONS: Young children who develop unprovoked seizures after a febrile seizure are at substantial risk for further seizures with fever. This may represent part of the spectrum of benign febrile seizures or it may represent the so-called "epilepsy triggered by fever" spectrum. It affects only a small proportion of children with febrile seizures; however, in some children, it may be useful information to consider when making treatment decisions.

Age of Onset↗

Serotyping Coxiella burnetii isolates from acute and chronic Q fever patients by using monoclonal antibodies.

Four mouse monoclonal antibodies reacting with Coxiella burnetti lipopolysaccharide antigens were produced and used in serotyping 17 C. burnetii isolates from acute Q fever and Q fever endocarditis patients in France. Two monoclonal antibodies (1B2 and 3B6) were considered specific for the Priscilla strain, a representative of Q fever endocarditis isolates, and did not react with the Nine Mile strain, which is representative of acute Q fever isolates. Monoclonal antibodies Nos. 1B2 and 3B6 reacted with 75% (3/4) acute Q fever isolates and 85% (11/13) of endocarditis isolates from France. It is reasonable to conclude that Priscilla-like strains cause both acute Q fever and Q fever endocarditis. The hypothesis that Priscilla-like strains only are associated with Q fever endocarditis should be reconsidered.

Acute Disease↗

Detection of Astrakhan fever rickettsia from ticks in Kosovo.

Astrakhan fever is a summer spotted fever resembling Mediterranean spotted fever, endemic in Astrakhan, a region of Russia located by the Caspian sea. Its agent is a spotted fever group rickettsia, member of the Rickettsia conorii complex, transmitted to humans by Rhipicephalus sanguineus and Rhipicephalus pumilio ticks. In Summer 2001, French United Nations troops in Kosovo collected 2 ticks on asymptomatic soldiers (1 R. sanguineus and 1 Hyalomma marginatum) and 10 ticks on dogs (7 R. sanguineus, 2 Ixodes ricinus, and 1 H. marginatum) in the Morina region. By PCR amplification of both the gltA and ompA genes, we detected a rickettsia in 4 R. sanguineus, i.e., 3 of those collected on dogs and those taken from military personnel. As ticks were preserved in alcohol, culture was not possible. The sequences obtained from these PCR products identified, with a 100% homology, Astrakhan fever rickettsia. None of the other collected tick species was positive. The patient with the positive tick remained asymptomatic. Our study demonstrates, for the first time, the presence of Astrakhan fever rickettsia in ticks outside Russia. We suspect that the area of distribution of this rickettsia could be wider than initially suspected. Moreover, as R. sanguineus ticks bite humans, Astrakhan fever might be a cause of spotted fever in Kosovo.

Animals↗

Route of administration differentially affects fevers induced by Gram-negative and Gram-positive pyrogens in rabbits.

We have investigated the febrile responses of New Zealand White rabbits to a Gram-negative pyrogen (bacterial lipopolysaccharide (LPS) from Salmonella typhosa), commonly associated with systemic infection, and a Gram-positive pyrogen (Staphylococcus aureus), more frequently associated with superficial soft tissue infection, each administered via one of four different routes (intravenous, intramuscular, subcutaneous or intraperitoneal) at each of three different doses (LPS: 0.1, 1 and 10 microg kg(-1); S. aureus: 1.5 x 10(7), 1.5 x 10(8) and 1.5 x 10(9) cell walls kg(-1)). Intravenous administration of LPS evoked rapid, dose-dependent biphasic fever. Injection of LPS by the other routes also evoked dose-dependent fever. However, these fevers were monophasic, had increased latency of onset, and were of lower amplitude. It is important to note that a dose of approximately 10 and 100 times that of the standard intravenous dose was required to produce a similar peak rise in temperature when administered subcutaneously and intraperitoneally, respectively. Intravenous injection of the highest dose of S. aureus evoked dose-dependent biphasic fever, with short latency of onset, which was very similar to that induced by intravenous LPS. At lower doses, intravenous S. aureus induced monophasic fever. No fever occurred when the same doses of S. aureus were administered by any other route. We conclude that any of the four routes may be used for the study of LPS-induced fever, provided that the doses are adjusted. However, studies of S. aureus-induced fever, and detection of contamination with either pyrogen, requires intravenous injection.

Animals↗

Central action sites of interleukin-1 beta for inducing fever in rabbits.

1. Intravenous (I.V.) human recombinant interleukin-1 beta (IL-1 beta) in high doses caused biphasic fever in rabbits. In lower doses it produced only the first phase of fever. 2. Intracerebroventricular (I.C.V.) or intrapreoptic-anterior hypothalamic (IPOAH) injection of IL-1 beta produced a rather rapid and marked increase in rectal temperature. 3. Subcutaneously administered indomethacin partly reduced the first phase and more substantially the second phase of the biphasic fever induced by high doses of I.V. IL-1 beta. The first phase may thus be prostaglandin independent at least in part. 4. In the fever induced by I.C.V. injection of IL-1 beta, subcutaneous indomethacin reduced the elevation of the rectal temperature considerably and delayed the onset of fever. Administration of indomethacin (I.C.V.) caused marked inhibition of the fever induced by a lower I.C.V. dose of IL-1 beta, but with a high dose the onset of the fever was delayed for about 1 h, without the total rise being affected. 5. It is concluded that the first phase of biphasic fever is caused by IL-1 beta acting via an extravascular component of the organum vasculosum laminae terminalis (OVLT) or the circumventricular organs accessible from only the blood side, to release arachidonate metabolites, presumably prostaglandin E2 (PGE2), and the second phase by IL-1 beta acting via the blood-brain interface accessible both from the blood side and the brain side, to release metabolites other than PGE2.

Animals↗

Is thermal scanner losing its bite in mass screening of fever due to SARS?

Severe acute respiratory syndrome (SARS) is a highly infectious disease caused by a coronavirus. Screening to detect a potential SARS infected person plays an important role in preventing the spread of SARS. The use of infrared thermal imaging cameras has been proposed as a noninvasive, speedy, cost effective and fairly accurate means for mass blind screening of potential SARS infected persons. Infrared thermography provides a digital image showing temperature patterns. This has been previously utilized in the detection of inflammation and nerve dysfunctions. It is believed that IR cameras can potentially be used to detect subjects with fever, the cardinal symptom of SARS, and avian influenza. The accuracy of the infrared system can, however, be affected by human, environmental, and equipment variables. It is also limited by the fact that the thermal imager measures the skin temperature and not the core body temperature. As known, the body determines a temperature as its so-called "set point" at any one time during the body temperature regulation. Fever happens if the hypothalamus detects pyrogens and then raises the set point. The time course of a typical fever can be divided into three stages. When the fever initiates, the body attempts to raise its temperature but vasoconstriction occurs to prevent heat loss through the skin. With this reason, some individuals at this stage of fever (at the rising slope and immediately after fever begins or falling slope after the fever breaks) will not be detected by the scanner if it is not designed to detect subject at the plateau of the fever (with her/his high core temperature) in particular. This paper aims to study the effectiveness of infrared systems for its application in mass blind screening to detect subjects with elevated body temperature. For this application, it is critical for thermal imagers to be able to identify febrile from normal subjects accurately. Minimizing the number of false positive and false negative cases, improves the efficiency of the screening stations. False negative results should be avoided at all costs, as letting a SARS infected person through the screening process may result in potentially catastrophic results. Various statistical methods such as linear regression, Receiver Operating Characteristics analysis, and neural networks based classification were used to analyze the temperature data collected from various sites on the face on both the frontal and side profiles. Two important conclusions were drawn from the analysis: the best region on the face to obtain temperature readings and the optimal preset threshold temperature for the thermal imager. To conclude, the current research application will remain an interest and useful for reference by both local and overseas manufacturers of thermal scanners, users, and various government and private establishments. As elevation of body temperature is a common presenting symptom for many illnesses including infectious diseases, thermal imagers are useful tools for mass screening of body temperature not only for SARS but also during other public health crisis where widespread transmission of infection is a concern.

Body Temperature↗

Effect of natriuretic peptide receptor antagonist on lipopolysaccharide-induced fever in rats: is natriuretic peptide an endogenous antipyretic?

We investigated whether natriuretic peptide (NP) acts as an endogenous antipyretic inside and/or outside the blood-brain barrier in rats made febrile by systemic administration of bacterial endotoxin (lipopolysaccharide; LPS). Intravenous (i.v.) injection of LPS induced a triphasic fever, the second phase of which was significantly enhanced by an i.v. injection of the NP receptor (A-type and B-type) antagonist HS-142-1, a glucose-caproic acid polymer. In contrast, the same antagonist (i.v.) had no effect on the fever induced by i.v. injection of interleukin (IL)-1beta. An i.v. administration of HS-142-1 enhanced the LPS (i.v.)-induced IL-1beta response in the rat spleen. An i.v. treatment with atrial NP (ANP) significantly attenuated the second phase of the LPS-induced fever. On the other hand, i.c.v. injection of the above-mentioned NP receptor antagonist resulted in an augmentation of the third phase of the fever induced by i.v. administration of LPS, the same phase that was attenuated by ANP given i.c.v. When given intracerebro-ventricularly (i.c.v.), the antagonist had no effect on the fever induced by i.v. IL-1beta. Finally, the fever induced by i.c.v. injection of LPS was not affected even by an i.c.v. administration of the antagonist. These results suggest that the production of pyrogenic cytokines (such as IL-1beta) that follows i.v. LPS injection may be inhibited by NP acting outside the blood-brain barrier, leading to an inhibition of the fever. In contrast, inside the blood-brain barrier NP may inhibit cytokine-independent mechanisms present within the rat brain that mediate LPS (i.v.)-induced fever.

Animals↗