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PubMed1974

Fever produced by endotoxin injected into the hypothalamus of the monkey and its antagonism by salicylate.

1. A suspension of the killed cell bodies of either E. coli, S. dysenteriae or S. typhosa was micro-injected through cannulae implanted chronically at specific sites within the diencephalon and mid-brain of the unanaesthetized monkey. A biphasic, monophasic or an undifferentiated fever could be induced by each type of micro-organism, but the type of response depended solely upon the locus of injection.2. Although little difference in the potency of the three pyrogens was found, the rise in body temperature was in each instance dependent upon the concentration of the endotoxin. A more intense fever was accompanied by shivering, vasoconstriction of the ear vessels, piloerection and huddling behaviour. Tolerance to the pyrexic effect of repeated injections of endotoxin did not develop.3. The febrile response having the shortest latency, greatest maximum rise in temperature and largest 10-hr fever index was evoked by micro-injections into the anterior hypothalamic, preoptic area. The incidence of biphasic fevers was also greater after endotoxin was injected into this same region. Endotoxin given similarly in the posterior hypothalamus or in the mesencephalon had either no effect or produced a smaller elevation in temperature after a longer latency. The distance of an injection site from the coronal plane formed by the optic chiasm and anterior commissure correlated significantly with the latency and magnitude of the temperature change as well as the fever index.4. When given intravenously, endotoxin in a quantity at least 100 times greater was required to evoke a fever similar to that produced when the pyrogen was micro-injected into the anterior hypothalamic, preoptic region. However, a biphasic fever was evoked with a latency of from 3 to 15 min when a larger amount of endotoxin was injected intravenously. Tolerance developed rapidly to the febrile effect of endotoxin administered by this route although toxic reactions were not observed.5. After the fever evoked by the hypothalamic injection of endotoxin had reached a plateau, 300-1200 mg sodium salicylate administered intragastrically produced a dose-dependent fall in temperature, but had no effect on the body temperature of an afebrile monkey.6. It is concluded that in the rhesus monkey, a bacterial pyrogen can evoke a fever which is mediated entirely by an action on the central nervous system, the principal site being the anterior hypothalamic, preoptic area. The first phase of a biphasic fever caused by bacteria acting either by the central or peripheral route seems to be due either to a direct action of the pyrogen on the cells of the anterior hypothalamus, or to the secondary release within this region of an intermediary thermogenic substance such as 5-hydroxytryptamine or prostaglandin. The finding that sodium salicylate counteracts a centrally evoked fever is not compatible with the hypothesis that an antipyretic exerts its action by preventing a pyrogen that is circulating in the blood stream from entering the central nervous system.

Animals↗
PubMed1988

Multiple control of fever production in the central nervous system of rabbits.

1. The effects of microinjection of prostaglandin D2, E2 and F2 alpha and of endogenous pyrogen on the rectal temperature of rabbits were extensively examined in sixty-eight brain regions and in the third cerebral ventricle. 2. Intracerebroventricular injection of both prostaglandins E2 and F2 alpha produced dose-dependent fever over a range of 100-1000 ng. The selective brain regions, the nucleus broca ventralis, preoptic area, anterior hypothalamus and the ventromedial hypothalamus, responded to microinjections of a small dose (less than 200 ng) of prostaglandins E2 and F2 alpha by producing fever. Furthermore, the lateral hypothalamus, ventral thalamus, substantia nigra and the trigeminal nucleus were also sensitive to high concentrations of prostaglandins E2 and F2 alpha, fever being produced. It is likely that prostaglandin D2 is not involved in fever induction. 3. The ventricular injection of endogenous pyrogen also produced fever. However, brain regions sensitive to microinjection of endogenous pyrogen were exclusively localized to regions near the organum vasculosum laminae terminalis (OVLT), such as the nucleus broca ventralis and the preoptic area. In contrast to the monophasic fever induced by prostaglandins E2 and F2 alpha, about 30 min after ventricular or cerebral injection of endogenous pyrogen the rectal temperature gradually started to rise and the fever was prolonged over 4 h. 4. We investigated the effect of an inhibitor of prostaglandin synthesis, sodium salicylate, on biphasic fever induced by intravenous injection of bacterial endotoxin. The microinjections of sodium salicylate into the bilateral regions near the OVLT suppressed the second peak but had no effect on the first peak. 5. The present study clarifies that there exist two separate mechanisms of induction of biphasic fever. Correlating with the first peak of biphasic fever, prostaglandins synthesized outside the blood-brain barrier act on multiple sites in the central nervous system to induce fever. Correlating with the second peak, endogenous pyrogen acts on regions near the OVLT to synthesize and release pyrogenic prostaglandins.

Animals↗
PubMed2004

Thermoeffector neuronal pathways in fever: a study in rats showing a new role of the locus coeruleus.

It is known that brain noradrenaline (norepinephrine) mediates fever, but the neuronal group involved is unknown. We studied the role of the major noradrenergic nucleus, the locus coeruleus (LC), in lipopolysaccharide (LPS)-induced fever. Male Wistar rats had their LC completely ablated electrolytically or their catecholaminergic LC neurones selectively lesioned by microinjection of 6-hydroxydopamine; the controls were sham-operated. Both lesions resulted in a marked attenuation of LPS (1 or 10 microg kg(-1), i.v.) fever at a subneutral (23 degrees C) ambient temperature (Ta). Because electrolytic and chemical lesions produced similar effects, the role of the LC in fever was further investigated using electrolytic lesions only. The levels of prostaglandin (PG) E2, the terminal mediator of fever, were equally raised in the anteroventral third ventricular region of LC-lesioned and sham-operated rats during the course of LPS fever, indicating that LC neurones are not involved in febrigenic signalling to the brain. To investigate the potential involvement of the LC in an efferent thermoregulatory neuronal pathway, the thermoregulatory response to PGE(2) (25 ng, i.c.v.) was studied at a subneutral (23 degrees C, when fever is brought about by thermogenesis) or neutral (28 degrees C, when fever is brought about by tail skin vasoconstriction) Ta. The PGE2-induced increases in metabolic rate (an index of thermogenesis) and fever were attenuated in LC-lesioned rats at 23 degrees C, whereas PGE2-induced skin vasoconstriction and fever normally developed in LC-lesioned rats at 28 degrees C. The LC-lesioned rats had attenuated PGE2 thermogenesis despite the fact that they were fully capable of activating thermogenesis in response to noradrenaline and cold exposure. It is concluded that LC neurones are part of a neuronal network that is specifically activated by PGE2 to increase thermogenesis and produce fever.

Animals↗
PubMed1989

A possible mechanism of fever induced by Nocardia rubra cell wall skeleton (N-CWS) in experimental animals.

The characteristics of fever elicited by the cell wall skeleton of Nocardia rubra (N-CWS) and by lipopolysaccharide (LPS) were compared in rabbits, and the possible involvement of the antigenicity of N-CWS was investigated in guinea pigs. In rabbits, fever of more than 0.5 degree C developed after an intravenous (i.v.) injection of 10 micrograms/kg or more of N-CWS, and was monophasic with 30-100 micrograms/kg but biphasic with the highest dose of 300 micrograms/kg. LPS elicited fever with similar characteristics at doses of 0.01-0.1 microgram/kg. With both compounds, the fever was inhibited by indomethacin. Tolerance to N-CWS and LPS appeared after dosing with 30 or 0.1 micrograms/kg, respectively for 10 d. In guinea pigs sensitized with N-CWS, challenge with 1 or 10 micrograms/kg of N-CWS 10 d later, which did not induce fever in the nonsensitized animals, caused fever of more than 0.5 degree C, and delayed-type hypersensitivity (DTH) appeared. N-CWS also elicited fever in nonsensitized guinea pigs bearing N-CWS-sensitized lymphocytes or anti-N-CWS antibody; the fever was higher in the guinea pigs sensitized with the lymphocytes than in those with the anti-N-CWS antibody. In brief, single injections of N-CWS and of LPS elicited fever with similar characteristics, although the potency of N-CWS was weaker. With N-CWS, the fever is proposed to be triggered by the antigenicity of the compound itself, because doses as low as 1 or 10 micrograms/kg elicited fever along with immunological response in N-CWS-sensitized animals, but not in nonsensitized ones.

Animals↗
PubMed2002

Q fever--still a query and underestimated infectious disease.

Coxiella burnetii (C.b.) is a strictly intracellular, Gram-negative bacterium. It causes Q fever in humans and animals worldwide. The animal Q fever is sometimes designated "coxiellosis". This infection has many different reservoirs including arthropods, birds and mammals. Domestic animals and pets, are the most frequent source of human infections. Q fever may appear basically in two forms, acute and chronic (persistent). The latter form of Q fever in animals is characteristic by shedding C.b. into the environment during parturition or abortion. Human Q fever results usually from inhalation of contaminated aerosols originating mostly from tissue and body fluids of infected animals. Q fever may appear in humans either in an acute form accompanied mainly by fever (pneumonia, flu-like disease, hepatitis) or in a chronic form (mainly endocarditis). Diagnosis of Q fever is based on isolation of the agent in cell culture, its direct detection, namely by PCR, and serology. Detection of high phase II antibodies titers 1-3 weeks after the onset of symptoms and identification of IgM antibodies are indicative to acute infection. High phase I IgG antibody titers >800 as revealed by microimmunofluorescence offer evidence of chronic C.b. infection. For acute Q fever, a two-weeks-treatment with doxycycline is recommended as the first-line therapy. In the case of Q fever endocarditis a long-term combined antibiotic therapy is necessary to prevent relapses. Application of Q fever vaccines containing or prepared from phase I C.b. corpuscles should be considered at least for professionally exposed groups of the population. Infections caused by C.b. are spread worldwide and may pose serious and often underestimated health problems in human but also in veterinary medicine. Though during the last decades substantial progress in investigation of C.b. has been achieved and many data concerning this pathogen has been accumulated, some questions, namely those related to the pathogenesis of the disease, remain open.

Acute Disease↗
PubMed1978

Viral haemorrhagic fevers of man.

This article reviews the current state of knowledge on the viral haemorrhagic fevers that infect man, namely smallpox, chikungunya fever, dengue fever, Rift Valley fever, yellow fever, Crimean haemorrhagic fever, Kyasanur Forest disease, Omsk haemorrhagic fever, Argentinian haemorrhagic fever (Junin virus), Bolivian haemorrhagic fever (Machupo virus), Lassa fever, haemorrhagic fever with renal syndrome, and Marburg and Ebola virus diseases.

Animals↗
PubMed1982

Effect of experimentally induced fever on mammary blood flow in lactating goats.

The effect of artificially induced fever on normal mammary blood flow (MBF) was studied in conscious lactating goats in a thermoneutral environment. Fever was induced either by intravenous (i.v.) injection of LPS or by intracerebroventricular (i.c.v.) infusion of PGE2. The increment stage of fever was always accompanied by a fall in MBF, shivers and miosis. There was a positive correlation between the intensity of temperature increase and MBF decrease. Once fever was established or during the decrement stage of fever, MBF returned to control levels and often increased far above pre-injection values. These specific circulatory changes observed in the lactating udder of the goat might contribute to the genesis and lysis of fever. MBF might play an important role in the pathogenesis of fever in the lactating goat. The effect of centrally induced fever was studied on the biphasic MBF pattern normally occurring during experimentally induced LPS mastitis. PGE2 was infused i.c.v. practically simultaneously with the intramammary administration of LPS. In most experiments fever occurred earlier than during control mastitis. The biphasic MBF-curve was strongly altered, MBF peak I being inhibited. Fever increment during control mastitis could be one of the factors limiting the duration of MBF peak I and fever decrement could induce peak II.

Animals↗
PubMed1994

National survey of pediatric fever management practices among emergency department nurses.

INTRODUCTION: Management of pediatric fever is controversial. Although many nursing texts advocate aggressive fever management, research provides evidence that fever is a normal physiologic process with beneficial effects. We sought to describe emergency nurses' pediatric fever management practices, their rationales for practice, and their practice consistency. METHODS: A researcher-developed tool was mailed to a systematic random sample of approximately 5% of ENA members. Surveys were mailed to 1136 nurses nationally; 731 surveys were returned (64% response rate). RESULTS: Temperature at which nurses initiate fever interventions varied from 37.8 degrees C (100 degrees F) to 40.6 degrees C (105 degrees F). Most frequently identified rationales for intervention were prevention of fever increase (83.3%), fever reduction (76.9%), comfort (74.7%), and seizure prevention (65.3%). Most nurses (79.8%) employ tepid sponging to reduce fever; 31% sponge routinely. Nurses reported sponging for temperatures higher than 38.9 degrees C (102 degrees F) to 40.6 degrees C (105 degrees F). Rationales for sponging included seizure prevention (58%), rapid cooling (56.8%), and treatment of fevers unresponsive to antipyretics (45.6%). Factors influencing rationales for practice included departmental standards of care (67.2%), physician practices (65.8%), and common sense (64.2%). DISCUSSION: The results of this nationwide survey demonstrate that fever management practices vary. ED nurses are practicing in a manner consistent with that advocated in many nursing texts but not necessarily the research literature. We believe that clinical trials of commonly used fever treatments are indicated. Standards of care could then be revised to reflect the research literature.

Adult↗
PubMed1994

Multidrug-resistant typhoid fever in Singapore.

A study was conducted to determine the clinical and epidemiological characteristics of multidrug-resistant (MDR) typhoid fever in Singapore. Twenty-one of 121 patients with typhoid fever had MDR typhoid fever after recent travel to the Indian subcontinent. Fifty patients with drug susceptible typhoid fever were also analysed for comparison. Nineteen of the MDR S. typhi isolates had resistance to ampicillin, chloramphenicol and trimethoprim-sulphamethoxazole (TMP-SMX) while the remainder had resistance to ampicillin and TMP-SMX. The predominant presenting symptoms were fever and diarrhoea. Eleven patients with MDR typhoid fever were treated with oral ciprofloxacin and nine with intravenous ceftriaxone. The patients with MDR typhoid fever had a longer duration of fever defervescence (8 +/- 5 days) compared to those with drug-susceptible typhoid fever (5.7 +/- 4.16 days) (p < 0.01). Eighteen patients were cured and one patient defaulted treatment. Two patients relapsed within two months of treatment. The study showed that 17.4% of patients with typhoid fever had imported MDR S. typhi after recent travel to the Indian subcontinent where MDR typhoid fever is prevalent.

Adult↗
PubMed1975

Study of the pattern of Widal test in infants and children; II. Pattern of Widal test in children with enteric fevers. An attempt to define the diagnostic titer for upper Egypt.

The study embodied 45 children with enteric fevers proved by bacteriological culture of blood, stools and urine and 20 children with rheumatic fever. Widal test was done for the rheumatic fever cases and was done repeatedly at weekly intervals for the enteric fever cases. The clinical features of children with enteric fevers was discussed. By contrasting the results of Widal test in children with enteric fever with the results in apparently normal infants and children from the same locality, a minimal diagnostic dual Widal titer was suggested. This combines "O" agglutinin in a titer of 1/160 provided that the other "H" agglutinins are at a lower titer. This suggested diagnostic titer improved the specificity of Widal test. This titer is encountered only in 0.58% of normal individuals and in none of 20 children with rheumatic fever. This titer also yielded an excellent sensitivity to diagnose actual enteric fever cases reaching up to 93.3%. Bacterial isolates from enteric fever cases were S. typhi in 55.5%, S. paratyphi A in 33.3% and S. paratyphi B in 11.1%. Chloramphenicol therapy resulted in a higher cure rate and a more rapid defervescence than ampicillin therapy. Regarding the effect of these antibiotic therapies on the rise of Widal agglutinin titers in children with enteric fevers there are two observations : 1--A four fold rise, is uncommon. A two fold rise is the common finding. 2--There is no consistent difference between chloramphenicol and ampicillin as regards their effect on the rise of agglutinin titers.

Ampicillin↗
PubMed1998

Mutual antagonism of rheumatoid arthritis and hay fever; a role for type 1/type 2 T cell balance.

OBJECTIVES: The balance between interferon gamma (IFN gamma) and interleukin 4 (IL4) producing T cells (T1 and T2 cells) seems to be of importance in many (auto)immune disorders. In general, T1 cell activity is important in cellular immunity whereas T2 cell activity plays a part in humoral responses. T1 cell activity predominates in joints of patients with rheumatoid arthritis (RA) whereas T2 cell activity is characteristic of atopic syndromes. This study investigated whether the prevalence of hay fever in RA is low and if severity of RA (T1 cell activity) can be influenced by the concomitant occurrence of a T2 cell mediated disease (hay fever). METHODS: The prevalence of hay fever was assessed in 643 consecutive (RA and non-RA) patients seen in our outpatient clinic and confirmed by skin test and specific IgE. Of this group the 12 RA patients with hay fever were compared with RA patients without hay fever (matched for age, sex, and disease duration). RESULTS: The prevalence of hay fever in RA patients is lower than in non-RA patients (4% versus 8%), and yields a relative risk for RA patients to develop hay fever of 0.48. RA patients with hay fever showed a lower disease activity (erythrocyte sedimentation rate, C reactive protein, Thompson joint score, and radiographic joint damage (Sharp) score) than RA patients without hay fever. The clinical data were related to peripheral blood T1/T2 cell balance: a lower IFN gamma/IL4 ratio was observed for RA patients with hay fever, indicating a comparatively increased T2 cell activity in RA patients with hay fever. CONCLUSION: These results argue in favour of the exploration of treatments aimed at regulation of a possible imbalance in T1/T2 cell activity in RA.

Adult↗
PubMed2002

Different slopes for different folks: socioeconomic and racial/ethnic disparities in asthma and hay fever among 173,859 U.S. men and women.

Although allergic diseases such as asthma and hay fever are a major cause of morbidity in industrialized countries, most studies have focused on patterns of prevalence among children and adolescents, with relatively few studies on variations in prevalence by race/ethnicity and socioeconomic position among adults. Our study examined racial/ethnic and socioeconomic patterns in the prevalence of asthma overall, asthma with hay fever, asthma without hay fever, and hay fever overall, in a population of 173,859 women and men in a large prepaid health plan in northern California. Using education as a measure of socioeconomic position, we found evidence of a positive gradient for asthma with hay fever with increasing level of education but an inverse gradient for asthma without hay fever. Hay fever was also strongly associated with education. Compared with their White counterparts, Black women and men were more likely to report asthma without hay fever, and Black women were less likely to have asthma with hay fever. Asian men were also more likely to report asthma with hay fever, and Asian women and men were much more likely to have hay fever. Racial/ethnic disparities in prevalence of allergic diseases were largely independent of education. We discuss implications for understanding these social inequalities in allergic disease risk in relation to possible differences in exposure to allergens and determinants of immunologic susceptibility and suggest directions for future research.

Adolescent↗
PubMedDate not supplied

[Plasmatic levels of interleukin-1beta and interleukin-6 in newborn infants with fever]

OBJECTIVE: To study plasma levels of IL-1beta and IL-6 in order to distinguish the presence of bacterial infection in newborn infants with fever. METHODS: A cohort of 117 newborn infants with postnatal age equal to or less than 5 days, with no previous use of antibiotic therapy, and with clinical suspicion of bacterial infection was studied from July 1995 through August 1996. Those with definite criteria for sepsis were considered infected. Fever was defined as axillar temperature > 37.5 degrees C in three independent measurements. The patients were classified in four different groups: Group 1: infected with fever; Group 2: infected without fever; Group 3: not infected with fever; Group 4: not infected without fever. Complete blood count, platelet count, blood or other fluid cultures, and plasmatic levels of IL-1beta and IL-6 were collected before the beginning of antibiotic therapy. RESULTS: Of the 117 newborn infants studied were 66 infected and 51 not infected. Fever was present in 45 (38.46%). The median values of IL-1beta and IL-6 were significantly higher in newborn infants with fever than in those with no fever. There were significant differences between groups 1 and 2, 1 and 4, and 2 and 3 for IL-1beta. There were no significant differences between groups 2 and 4, and 1 and 3 for IL-1beta. Eight (72%) newborn infants with no infection and no fever had environment heating, and 3 had dehydration. There were no differences in median IL-6 levels between groups 1 and 2, and 3 and 4. There were significant differences in the median IL-6 levels between groups 1 and 3, and 1 and 4. CONCLUSIONS: IL- 6 is a marker of early neonatal sepsis. IL-1beta is related to neonatal fever response independently of the presence of bacterial infection.

Journal Article↗
PubMedDate not supplied

Dengue Fever in travelers returning from southeast Asia.

BACKGROUND: Dengue fever is an important illness facing travelers from nonendemic to endemic countries. METHODS: We reviewed 696 consecutive returned travelers managed at an Australian tertiary-care hospital for an illness acquired overseas. Patients with dengue fever were compared to those with a dengue-like illness, malaria, typhoid fever and rickettsial infections. RESULTS: In total, 19 cases of dengue fever and 20 cases of dengue-like illness were diagnosed, with 85% of cases acquired in Asia. The most common presenting features of dengue were fever (100%), myalgia (79%), rash (74%), headache (68%), nausea (37%), and diarrhea (37%). Compared to those with malaria, typhoid fever and rickettsial infections, patients with dengue were significantly more likely to have myalgia and a temperature <39 degrees C. Compared to all other illnesses in our returned travelers, dengue fever was 18 times more likely if fever and leukopenia were present, 71 times if fever and rash were present, and 230 times if fever, rash and leukopenia were present. All patients with dengue recovered completely. CONCLUSIONS: Dengue fever is an important health problem for travelers not only to Southeast Asia but to all endemic countries. The prevalence appears to be increasing in travelers, and health care professionals need to be familiar with its presentation in travelers. The clinical presenting features provide important guides to establishing the diagnosis.

Adolescent↗
PubMed1977

Milk fever in dairy cows. VIII. Effect of injected vitamin D3 and calcium and phosphorus intake on incidence.

In a field trial, effects of prepartal intermuscular injection of 10 million units of vitamin D3 on incidence of milk fever were examined both in relation to intake of calcium and phosphorous during the dry period and previous history of milk fever. Based upon intake of calcium and phosphorus cooperating herds were grouped as feeding: 1) greater than .53% of the total ration dry matter as calcium and greater than .28% as phosphorus: 2) less than .47% as calcium and greater than .28% as phosphorus; 3) greater than .47% to less than .53% as calcium and greater than .22% to less than .28% as phosphorus. Injections of vitamin D3 given approximately 1 wk prepartum reduced incidence of milk fever in cows with previous history of milk fever in all three groups but had no effect in cows with no previous milk fever. Incidence of milk fever was lower in group 3 than for cows of groups 1 and 2 with previous milk fever and than for cows of group 1 with no previous history. The results indicate that careful control of calcium and phosphorus intake during the dry period at .5% calcium and .25% phosphorus of the dry matter of the total ration will limit milk fever incidence to about 10%. Injections of vitamin D3 as described will reduce inicidence of milk fever further in cows with previous milk fever but not in cows with no previous milk fever.

Animals↗
PubMed1995

Nucleotide sequence variation of the envelope protein gene identifies two distinct genotypes of yellow fever virus.

The evolution of yellow fever virus over 67 years was investigated by comparing the nucleotide sequences of the envelope (E) protein genes of 20 viruses isolated in Africa, the Caribbean, and South America. Uniformly weighted parsimony algorithm analysis defined two major evolutionary yellow fever virus lineages designated E genotypes I and II. E genotype I contained viruses isolated from East and Central Africa. E genotype II viruses were divided into two sublineages: IIA viruses from West Africa and IIB viruses from America, except for a 1979 virus isolated from Trinidad (TRINID79A). Unique signature patterns were identified at 111 nucleotide and 12 amino acid positions within the yellow fever virus E gene by signature pattern analysis. Yellow fever viruses from East and Central Africa contained unique signatures at 60 nucleotide and five amino acid positions, those from West Africa contained unique signatures at 25 nucleotide and two amino acid positions, and viruses from America contained such signatures at 30 nucleotide and five amino acid positions in the E gene. The dissemination of yellow fever viruses from Africa to the Americas is supported by the close genetic relatedness of genotype IIA and IIB viruses and genetic evidence of a possible second introduction of yellow fever virus from West Africa, as illustrated by the TRINID79A virus isolate. The E protein genes of American IIB yellow fever viruses had higher frequencies of amino acid substitutions than did genes of yellow fever viruses of genotypes I and IIA on the basis of comparisons with a consensus amino acid sequence for the yellow fever E gene. The great variation in the E proteins of American yellow fever virus probably results from positive selection imposed by virus interaction with different species of mosquitoes or nonhuman primates in the Americas.

Aedes↗
PubMed2007

A retrospective review of 226 hospitalized patients with fever.

OBJECTIVE: To describe characteristics and outcomes for patients hospitalized with fever, not only patients with fever of unknown origin (FUO). METHODS: Medical records were reviewed for 226 consecutive patients hospitalized in a Japanese referral hospital with fever as one of the clinical problems. RESULTS: Although the majority of illnesses involved some sort of infection (54%), noninfectious inflammatory diseases, particularly adult Still's disease (n=6) and primary vasculitis syndromes (n=5) including 3 cases of Behçet's disease, represented the leading cause in patients who met the definition of FUO [16/51(31%)]. Tuberculosis (n=6) and psychological disorders (n=6) were associated with late diagnosis. However, there was only one patient meeting the definition of FUO among those with a psychological disorder. Among the patients with prolonged fever who did not strictly meet the definition of FUO, there was a considerable number of patients with critical illnesses, such as intra-abdominal abscess, polymyalgia rheumatica, sarcoidosis, ulcerative colitis, Castleman's disease, hematological and solid malignancies, and panhypopituitarism. Drug-induced fever, systemic viral infection and unspecified vasculitis were difficult to definitively diagnose, although these pathologies were suspected as causes of fever. Follow-up of patients without definitive diagnosis at discharge confirmed that the fever subsided spontaneously or the cause of fever was properly treated after diagnosis in every patient and that none died of the underlying febrile illness. CONCLUSIONS: The present findings, from all patients displaying fever at hospitalization, are in agreement with findings from prior FUO series. Strict use of the definition of FUO is thus unwarranted when managing patients with prolonged fever.

Adult↗
PubMed1996

Cascade of fever production in mice infected with influenza virus.

The cascade of fever production in influenza was studied. To analyse fever production in a murine model, we selected DBA/2 mice that have the highest susceptibility in fibrile responses among seven mouse strains. Intranasal influenza infection- and interferon (IFN)-induced fever production was studied in this mouse model. Fever was induced prominently on day 2 after influenza infection and IFN activity was also increased in serum. Only the level of interleukin (IL)-1 alpha, an endogenous pyrogen, rose markedly in serum among cytokines (IL-1 alpha, IL-2, IFN-gamma, and tumor necrosis factor-alpha) examined. Fever was induced 14 hr after intraperitoneal IFN-alpha treatment and IL-1 alpha level rose significantly in the serum of the IFN-alpha-treated mice as compared with that of untreated mice. Fever production was significantly suppressed by treatment with anti-IFN-alpha/beta or anti-IL-1 alpha antibody in infected mice and the former significantly suppressed responsive IL-1 alpha production, indicating that elevated IFN activity induced IL-1 alpha production and subsequently fever production in infected mice. The activity of cyclooxygenase (COX) that produces prostaglandin (PG)E2 was significantly augmented in the brain of infected mice on day 2 after infection. Fever production was suppressed by the inhibition of COX activity with aspirin, although IL-1 alpha level was maintained at the elevated level. Therefore, influenza infection in mice turned on the following cascade for fever induction: IFN production, IL-1 alpha production, elevated COX activity, and PGE2 production. We elucidated the relationship among IFN activity, IL-1 alpha production and COX activity and demonstrated the cascade of fever production in influenza infection.

Animals↗