Fever Response Research Articles

Interleukin-1 function and role in rheumatic disease.

Interleukin (IL)-1, first described ∼35 years ago as a secreted product of monocytes and neutrophils, refers to IL-1α and IL-1β, two key cytokines in the activation of innate immunity. These cytokines were among the first proteins identified as orchestrators of leukocyte communication, creating the class of secreted products now known as interleukins. The IL-1 family comprises a total of 11 members, including the two activating cytokines IL-1α and IL-1β as well as an inhibitory mediator, the IL-1 receptor antagonist. IL-1 is processed and activated by a caspase-1 dependent mechanism in conjunction with inflammasome assembly, as well as by caspase-1 independent processes that involve neutrophil proteases. Once activated, IL-1α and IL-1β act as potent proinflammatory cytokines at the local level, triggering vasodilatation and attracting monocytes and neutrophils to sites of tissue damage and stress. Importantly, these cytokines are crucial for the induction of matrix enzymes and serve as potent mediators of tissue damage by altering cartilage and bone homeostasis. Systemically, IL-1 cytokines foster the hypothalamic fever response and promote hyperalgesia. Uncontrolled IL-1 activation is a central component of some inflammatory diseases, including rare hereditary syndromes with mutations in inflammasome-associated genes or more frequent diseases such as gout, characterized by neutrophil infiltration and IL-1 activation. Apart from these connections to inflammatory diseases, an important role for IL-1 in inflammatory atherogenesis is also predicted. To date, four potent inhibitors of IL-1 are available for clinical use or in late-stage clinical development, which not only constitute efficacious therapies, but also helped improve our understanding of the role of IL-1 in human disease.

Limitations of the rabbit pyrogen test for assessing meningococcal OMV based vaccines.

The rabbit pyrogen test was developed in the early 1900's to detect contaminating pyrogens in parenteral medicines. Since its conception alternative methods with improved sensitivity, relevancy and which are ethically more acceptable have been developed. However, the test is a current Pharmacopeial method and is used to evaluate the pyrogen content of some vaccines. In this article the limitations and pitfalls of using the test to measure pyrogenicity of vaccines containing outer membrane vesicles are described. The method is unsuitable as a safety test for these products due to the high levels of endotoxin present in the vaccine which generate a pyrogenic response in rabbits when delivered intravenously without any dilution. Its use as a consistency test is also ambiguous as the test gives a qualitative rather than quantitative response and the rabbit models are highly variable. In addition there is evidence that measuring the temperature rise of the animals over three hours does not capture the maximum fever response. Finally the article considers the use of alternative methods and the validity of animal models when applying a consistency based approach for assessing the quality of licensed products.

Drosophila melanogaster does not exhibit a behavioural fever response when infected with Drosophila C virus.

Behavioural fever is a widely conserved response to infection. The host increases body temperature (Tb) by altering their preferred temperature (Tp), generating a fever and delaying or avoiding pathogen-induced mortality. This response is not ubiquitous in insects, however, although few studies have investigated this response to viral infection. Here, we examined the change in Tp of Drosophila in response to virus infection using a thermal gradient. No difference in Tp was observed. We suggest that the lack of behavioural fever could be due to the increased energy cost of maintaining a higher Tb whilst the immune response is active. To the best of our knowledge, this is the first study to assay for changes in Tp of infected Drosophila.

Fish can show emotional fever: stress-induced hyperthermia in zebrafish.

Whether fishes are sentient beings remains an unresolved and controversial question. Among characteristics thought to reflect a low level of sentience in fishes is an inability to show stress-induced hyperthermia (SIH), a transient rise in body temperature shown in response to a variety of stressors. This is a real fever response, so is often referred to as ‘emotional fever’. It has been suggested that the capacity for emotional fever evolved only in amniotes (mammals, birds and reptiles), in association with the evolution of consciousness in these groups. According to this view, lack of emotional fever in fishes reflects a lack of consciousness. We report here on a study in which six zebrafish groups with access to a temperature gradient were either left as undisturbed controls or subjected to a short period of confinement. The results were striking: compared to controls, stressed zebrafish spent significantly more time at higher temperatures, achieving an estimated rise in body temperature of about 2–4°C. Thus, zebrafish clearly have the capacity to show emotional fever. While the link between emotion and consciousness is still debated, this finding removes a key argument for lack of consciousness in fishes.

Induced systemic listeriosis in Alectoris chukar chicks: clinical, histopathological and microbiological findings

1. Systemic listeriosis was induced in 14-d-old Chukar partridge chicks, Alectoris chukar, by intravenous injection of a suspension containing 106 cfu/ml of viable Listeria monocytogenes organisms to study the course of infection.2. Septicaemic and encephalitic forms of listeriosis were observed in all birds. Infection resulted in a fever response 8-h post-inoculation. Disease rapidly developed over a 24-h period with decreased activity, lethargy, ruffled feathers, huddling, listlessness, inability to stand, wing droop, decreased feed and water consumption, growth depression, neural disturbances and finally death. Gross and histopathological changes were observed in the myocardium, proventriculus, gizzard, intestine, pancreas, kidney, liver, spleen, lung, meninges and joints.3. The diversity of these clinical signs and lesions suggests a high susceptibility of Chukar partridge chicks to systemic listeriosis.

Issues of Scientific and Practical Support of Anti-Epidemic Activities in the Course of Ebola Virus Disease Epidemic Response in West Africa

Consideration is given to the experience of cooperation between the Russian Federation and the Republic of Guinea in the matter of Ebola fever response. Outlined are the challenging issues regarding scientific support of preventive activities. Provided is a brief characteristic of Pasteur Institute of Guinea as a unique platform for research activities. Covered are the legal aspects of collaboration and priority areas for the development of common initiatives in the sphere of epidemiological monitoring. Identified are the stages of material reinforcement and medical stuff capacity building, including training of specialists with a view to the establishment of effective system for epidemiological surveillance.

Kinetics of pro-inflammatory cytokines, interleukin-10, and virus neutralising antibodies during acute ephemeral fever virus infections in Brahman cattle

While fever and inflammation are hallmark features of bovine ephemeral fever (BEF), the cytokine networks that underlie the acute phase of the disease have not been empirically defined in cattle. This study characterised the plasma kinetics of proinflammatory cytokines (IL-1β, IL-6, TNF-α) and IL-10 during acute BEF and elucidated on the relationship between the onset of the virus neutralizing antibody response and resolution of viraemia in natural BEF virus (BEFV) infections in cattle. Plasma from three BEFV-infected and three uninfected cattle was tested for the study cytokines by a cELISA, viraemia monitored by qRT-PCR, and virus neutralizing antibody titres determined using a standard protocol. Unlike the negative controls, plasma concentrations of IL-1β, TNF-α, IL-6, and IL-10 were consistently increased in the three virus-infected animals. Two of the infected heifers were recumbent and pyrexic on the first day of monitoring and increased cytokine production was already in progress by the time viraemia was detected in all the three infected animals. In all the virus-infected heifers, IL-1β was the most strongly expressed cytokine, IL-6 and IL-10 manifested intermediate plasma concentrations while TNF-α was the least expressed and demonstrated bi-phasic peaks three and five days after the onset of pyrexia. In two of the BEFV-infected heifers, viraemia resolved on the day of seroconversion while in the other infected animal, viral RNA was detectable up to three days after seroconversion. The present data document variable increase in plasma IL-1β, IL-6, TNF-α, and IL-10 during natural BEFV infections and the fact that upregulation of all but TNF-α precedes seroconversion. In addition to virus neutralising antibodies, it is likely that cytokine-mediated cellular mechanisms may be required for resolution of viraemia in BEF. Considering the anti-inflammatory properties of IL-10, its upregulation may potentially antagonise the fever response in BEFV-infected cattle.

No fever and leucocytosis in response to a lipopolysaccharide challenge in an insectivorous bat.

Bat immune systems may allow them to respond to zoonotic agents more efficiently than other mammals. As the first line of defence, the taxonomically conserved acute phase immune reaction of leucocytosis and fever is crucial for coping with infections, but it is unknown if this response is a key constituent to bat immunological success. We investigated the acute phase reaction to a standard lipopolysaccharide (LPS) challenge in Pallas's mastiff bats (Molossus molossus). Challenged bats lost mass, but in contrast to other mammals showed no leucocytosis or fever. There also was no influence on body temperature reduction during torpor. When compared to recent genome-wide assays for constituent immune genes, this lack of a conserved fever response to LPS contributes to a clearer understanding of the innate immune system in bat species and of the coevolution of bats with a wide diversity of pathogens.

Monoacylglycerol Lipase Regulates Fever Response.

Cyclooxygenase inhibitors such as ibuprofen have been used for decades to control fever through reducing the levels of the pyrogenic lipid transmitter prostaglandin E2 (PGE2). Historically, phospholipases have been considered to be the primary generator of the arachidonic acid (AA) precursor pool for generating PGE2 and other eicosanoids. However, recent studies have demonstrated that monoacyglycerol lipase (MAGL), through hydrolysis of the endocannabinoid 2-arachidonoylglycerol, provides a major source of AA for PGE2 synthesis in the mammalian brain under basal and neuroinflammatory states. We show here that either genetic or pharmacological ablation of MAGL leads to significantly reduced fever responses in both centrally or peripherally-administered lipopolysaccharide or interleukin-1β-induced fever models in mice. We also show that a cannabinoid CB1 receptor antagonist does not attenuate these anti-pyrogenic effects of MAGL inhibitors. Thus, much like traditional nonsteroidal anti-inflammatory drugs, MAGL inhibitors can control fever, but appear to do so through restricted control over prostaglandin production in the nervous system.

Fungi That Infect Insects: Altering Host Behavior and Beyond.

Approximately 1,000 species of the fungal phyla Microsporidia, Chytridiomycota, Entomophthoromycota (order: Entomophthorales), Basidiomycota, and Ascomycota are known to infect and kill insects [1]. Of these, species such as Beauveria bassiana and Metarhizium robertsii (Ascomycota: Hypocreales) are well-studied models for exploring the mechanisms of fungus–insect physiological interactions, and they are used as biological controls for insect pests [2]. Entomopathogenic Hypocreales are phylogenetically closely related to plant pathogens and endophytes [3], and their sexual stages belong to Cordyceps sensu lato [4]. However, these species are taxonomically diverse and differ from each other considerably in their genomic features [5–8] and, consequently, their host ranges, infection cycles, and life strategies. Fungal infection normally, but not always, results in the death of an insect in situ. The parasitic fungi such as the host-specific pathogen Ophiocordyceps unilateralis sensu lato can control insect brains and manipulate their behavior to reach death locations that are optimal for spore dispersal, the so-called fungal extended phenotype [9]. On the other hand, on top of physiological immune surveillance, insects (especially social insects such as ants and termites) can smell and avoid fungal pathogens, groom each other to clear pathogenic spores, generate a fever response, or die well away from their nestmates, which is termed behavioral or social immunity [10,11]. Either side of these interactions will benefit from behavioral changes in insects that maximize their adaptive fitness. In this paper, both types of insect behavior alternations are reviewed, and the underlying mechanisms are discussed.

Polysaccharide peptide from Coriolus versicolor induces interleukin 6-related extension of endotoxin fever in rats

Purpose: Polysaccharide peptide (PSP) extracted from the Coriolus versicolor mushroom is frequently suggested as an adjunct to the chemo- or radiotherapy in cancer patients. In a previous study we showed that PSP induced a tumour necrosis factor-α (TNF-α)-dependent anapyrexia-like response in rats. Thus, PSP appears to be a factor which modifies a number of pathophysiological responses. Because of this, PSP is suggested as a potential adjuvant for cancer therapy during which cancer patients frequently contract microbial infections accompanied by fever. The aim of the present study was to investigate whether or not PSP can modulate the course of the fever in response to an antigen such as lipopolysaccharide (LPS). Materials and methods: Body temperature (Tb) of male Wistar rats was measured by biotelemetry. PSP was injected intraperitoneally (i.p.) at a dose of 100 mg kg−1, 2 h before LPS administration (50 µg kg−1, i.p.). The levels of interleukin (IL)-6 and TNF-α in the plasma of rats were estimated 3 h and 14 h post-injection of PSP using a standard sandwich ELISA kit. Results: We report that i.p. pre-injection of PSP 2 h before LPS administration expanded the duration of endotoxin fever in rats. This phenomenon was accompanied by a significant elevation of the blood IL-6 level of rats both 3 h and 14 h post-injection of PSP. Pre-treatment i.p. of the rats with anti-IL-6 antibody (30 µg/rat) prevented the PSP-induced prolongation of endotoxin fever. Conclusions: Based on these data, we conclude that PSP modifies the LPS-induced fever in IL-6-related fashion.

Fever and the thermal regulation of immunity: the immune system feels the heat.

Fever is a cardinal response to infection that has been conserved in warm-blooded and cold-blooded vertebrates for more than 600 million years of evolution. The fever response is executed by integrated physiological and neuronal circuitry and confers a survival benefit during infection. In this Review, we discuss our current understanding of how the inflammatory cues delivered by the thermal element of fever stimulate innate and adaptive immune responses. We further highlight the unexpected multiplicity of roles of the pyrogenic cytokine interleukin-6 (IL-6), both during fever induction and during the mobilization of lymphocytes to the lymphoid organs that are the staging ground for immune defence. We also discuss the emerging evidence suggesting that the adrenergic signalling pathways associated with thermogenesis shape immune cell function.

A second wave of monocyte expansion may contribute to the severe dengue in 2014 outbreak in China (HUM4P.272)

Abstract The 2014 dengue outbreak, the largest one in the last ten years in China, resulted in 13,800 hospitalized patients and more than 300 severe dengue cases in Guangzhou. Both of the viral strain and the host immune background may contribute to severe dengue. Here we report the monocyte response in dengue fever (DF) and severe dengue (SD) during the acute infection of seven dengue patients (DF n=4 and SD n=3) using multiparameter flow-cytometry with a panel of 9-surface markers. We also compared dengue specific IgG, IgM and NS1 in serum at the same time points for each patient. Six of the seven patients were diagnosed as secondary DENV1 infection, while one DF diagnosed as primary DENV1 infection. NS1 was nearly cleared in all patients when the serum IgG and IgM reached the high level at day 8-10 from the onset of fever. Obvious monocyte expansion was observed in both of DF and SD groups, frequently companied with the expansion of CD14++CD16+ subset. But the pattern of the response in the two groups was different at the recovery phase. The monocyte expansion in DF group maintained at a high level at day 7-10. Interestingly, the SD group underwent a second wave of monocyte expansion, in parallel with clinical course, starting from day 7 to day 10, especially the CD16+CD64+ monocyte subset. The characteristics of monocyte responses in DF and SD groups will advance our understanding of human dengue pathogenesis and may implicate the potential targets for early therapy.

Abstract 44: Uveitis As An Important Ocular Sign To Help Early Diagnosis In Kawasaki Disease

Purpose: Atypical or incomplete Kawasaki disease (KD) frequently leads to delay in diagnosis and treatment. Delayed diagnosis is associated with increased risk of coronary artery aneurysm. Anterior uveitis peaks about a week after the onset of fever. The purpose of this study was to assess the differences in laboratorial findings including echocardiographic measurements, clinical characteristics such as duration of fever and treatment responses between KD patients with and without uveitis. Materials and Methods: 106 KD patients were studied from January 2008 to June 2013. Study group (n=28, KD with uveitis) was compared with control group (n=78, KD without uveitis). Laboratory data were obtained from each patients including complete blood count (CBC), erythrocyte sedimentation rate (ESR), platelet count, alanine aminotransferase (ALT), aspartate aminotransferase (AST), serum total protein, albumin, C-reactive protein (CRP), brain natriuretic peptide (BNP). Echocardiographic measurement and intravenous immunoglobulin responses were compared between two groups. Result: The incidence of uveitis was 26.4%. Neutrophil counts were higher in the uveitis group compared with the control group (64.3±15.8(х10 3 /mm 3 ) vs. 54.4±19.3 (х10 3 /mm 3 )). The age of patients was higher in the uveitis group compared with the control group (40.5±21.4 months vs. 33.4±29.3 months). ESR (43.3±27.2 mm/hr vs. 30.8±24.6 mm/hr) and CRP (8.1±6.1 mg/dL vs. 7.9±10.7mg/dL) were slightly increased in the uveitis group compared with the control group, but there was no significant difference between the two groups. Coronary artery diameter was slightly increased in the uveitis group but there was no significant difference between the two groups. There were no significant differences in duration of fever, BNP, coronary arterial complication and treatment responses between the two groups. Conclusion: Uveitis is the one of the important ocular signs to diagnose incomplete KD. It is significantly associated with the patient’s age and neutrophil count but not with the other laboratory measurements, coronary arterial complication or treatment responses.

Prostaglandin D2 modulates calcium signals induced by prostaglandin E2 in neurons of rat dorsal root ganglia

Fever in response to a localized subcutaneous stimulation with a low dose of lipopolysaccharide (LPS) can be attenuated by co-administration of a local anesthetic or the non-selective cyclooxygenase (COX) inhibitor diclofenac at doses, which do not exert systemic effects when injected at sites remote from the area of inflammatory stimulation. These results suggest a participation of neuronal afferent signals mediated by COX-products in the manifestation of fever under these conditions. We therefore, measured intracellular Ca2+-concentrations in cultured neurons from rat dorsal root ganglia (DRG) stimulated with the pyrogenic mediator prostaglandin E2 (PGE2), the anti-inflammatory and antipyretic mediator PGD2, mixtures of both PGs, and menthol using the fura-2 ratio imaging technique. Neurons could be grouped according to their size with diameters of about 15μm (small), 35μm (medium sized), or 55μm (large). 96 out of 264 neurons responded to PGE2 with pronounced Ca2+-signals, 53 of them being also responsive to menthol, indicative of their function as cold-sensors. 80% of these neurons belonged to the medium sized group. In a next experiment, we tested whether Ca2+-signals of PGE2 responsive neurons were modulated by PGD2. In 60% of all neurons investigated (n=57), the strength of the PGE2-induced Ca2+-signals was reduced by co-administration of PGD2. This effect was also observed in those neurons that were responsive to PGE2 and menthol (n=23; p<0.001). This observation indicates antagonistic effects of PGE2 and PGD2 on a neuronal pathway that involves cold sensors and is activated during a localized subcutaneous inflammation. This finding might provide an explanation for the reported antipyretic and anti-inflammatory capacities of PGD2.

Urinary Tract Infection: How It Happens?

Urinary tract infections (UTIs), including cystitis and pyelonephritis, affect a large proportion of the world population and account for substantial morbidity and medical costs. Classification of the UTIs is based on the anatomical level of infection, the grade of severity of infection, the underlying risk factors, and the microbiological findings. Uropathogenic Escherichia coli is the causative agent in 70-95% of community-acquired uroinfections and about 50% of all cases of nosocomial uroinfections. Virulence factors associated with uropathogenic strains of E. coli contain toxins such as haemolysin and cytotoxic necrotising factor, capsules, lipopolysaccharide, the siderophore aerobactin, and adhesive organelles. The ability to attach to urothelial cells is the most important determinant of pathogenicity. An adherence is followed by inflammation involving the urothelial cells’ cytokine response. Whereas interleukin (IL)-6 can cause the fever and systemic response of the UTIs, IL-8 can function as a neutrophil chemoattractant. Cytokines released by T cells and monocytes modify initiative urothelial cells’ cytokine response to bacteria. Nevertheless, antibiotic treatments can effectively sterilise the urine, but bacteria can survive and persist in the bladder tissue, serving as a reservoir for the recurrent UTIs. The severity of UTI reflects the quality and magnitude of the host response. While strong local and systemic innate immune activation occurs in patients with acute pyelonephritis, the response to asymptomatic bacteriuria is low. It should be reasonable to ‘individualise’ diagnosis and therapy by interconnecting information on uropathogenic bacterial virulence and the host response.

Analysis of Long-Term Temperature Variations in the Human Body.

Body temperature is a continuous physiological variable. In normal healthy adults, oral temperature is estimated to vary between 36.1°C and 37.2°C. Fever is a complex host response to many external and internal agents and is a potential contributor to many clinical conditions. Despite being one of the foremost vital signs, temperature and its analysis and variations during many pathological conditions has yet to be examined in detail using mathematical techniques. Classical fever patterns based on recordings obtained every 8-12 h have been developed. However, such patterns do not provide meaningful information in diagnosing diseases. Because fever is a host response, it is likely that there could be a unique response to specific etiologies. Continuous long-term temperature monitoring and pattern analysis using specific analytical methods developed in engineering and physics could aid in revealing unique fever responses of hosts and in different clinical conditions. Furthermore, such analysis can potentially be used as a novel diagnostic tool and to study the effect of pharmaceutical agents and other therapeutic protocols. Thus, the goal of our article is to present a comprehensive review of the recent relevant literature and analyze the current state of research regarding temperature variations in the human body.

Integrative genomics identifies 7p11.2 as a novel locus for fever and clinical stress response in humans.

Fever predicts clinical outcomes in sepsis, trauma and during cardiovascular stress, yet the genetic determinants are poorly understood. We used an integrative genomics approach to identify novel genomic determinants of the febrile response to experimental endotoxemia. We highlight multiple integrated lines of evidence establishing the clinical relevance of this novel fever locus. Through genome-wide association study (GWAS) of evoked endotoxemia (lipopolysaccharide (LPS) 1 ng/kg IV) in healthy subjects of European ancestry we discovered a locus on chr7p11.2 significantly associated with the peak febrile response to LPS (top single nucleotide polymorphism (SNP) rs7805622, P = 2.4 × 10(-12)), as well as with temperature fluctuation over time. We replicated this association in a smaller independent LPS study (rs7805622, P = 0.03). In clinical translation, this locus was also associated with temperature and mortality in critically ill patients with trauma or severe sepsis. The top GWAS SNPs are not located within protein-coding genes, but have significant cis-expression quantitative trait loci (eQTL) associations with expression of a cluster of genes ∼400 kb upstream, several of which (SUMF2, CCT6A, GBAS) are regulated by LPS in vivo in blood cells. LPS- and cold-treatment of adipose stromal cells in vitro suggest genotype-specific modulation of eQTL candidate genes (PSPH). Several eQTL genes were up-regulated in brown and white adipose following cold exposure in mice, highlighting a potential role in thermogenesis. Thus, through genomic interrogation of experimental endotoxemia, we identified and replicated a novel fever locus on chr7p11.2 that modulates clinical responses in trauma and sepsis, and highlight integrated in vivo and in vitro evidence for possible novel cis candidate genes conserved across human and mouse.

Effects of ovariectomy on the inflammatory responses of female rats to the central injection of lipopolysaccharide.

It has been reported that obesity leads to more marked inflammatory responses in a site-specific manner. As has been seen in other animal models of obesity, ovariectomized rodents exhibit obesity and exacerbated fever and anorectic responses to the systemic injection of lipopolysaccharide (LPS). Furthermore, they also display increased pro-inflammatory cytokine expression in several central and peripheral tissues. Interestingly, the alterations observed in the hypothalamus are more marked than those seen in other peripheral tissues. In this study, the effects of ovariectomy on hypothalamic inflammatory responses were evaluated using the central LPS injection method. LPS was intracerebroventricularly (i.c.v.) injected into ovariectomized and gonadally intact female rats, and the immune responses of the two groups were compared. The ovariectomized rats exhibited heavier body weights than the gonadally intact rats. In addition, the ovariectomized rats displayed stronger febrile responses than the gonadally intact rats. After the i.c.v. injection of LPS, the hypothalamic interleukin (IL)-1β, IL-6, and cyclooxygenase 2 mRNA levels of the ovariectomized rats were significantly higher than those of the gonadally intact rats. The effects of estradiol supplementation on the rats' immune responses were also examined. However, the febrile responses and hypothalamic IL-1β, IL-6, and TNF-α mRNA levels of estradiol-supplemented ovariectomized rats and body weight matched oil-administered (control) rats did not differ after the i.c.v. injection of LPS. These results indicate that hypothalamic sensitivity to LPS is increased in ovariectomized rats and that this change is induced by the indirect effects of gonadal steroid deficiency. As is seen in other obese animal models, ovariectomy-induced obesity might play important roles in the exacerbated inflammatory responses observed in ovariectomized rats.

Preliminary analysis of the transcriptome of salivary glands of Ornithodoros brasiliensis (Acari: Argasidae)

Ornithodoros brasiliensis Aragao is an endemic tick to Brazil, restricted to highlands of the state of Rio Grande do Sul[1]. It is a very aggressive species to humans, causing fever, great pain and intense inflammatory response at the bite site[2]. To build a cDNA library from the salivary glands of this tick. Pirosequencing was used, Model GS-454 Junior to sequencing the cDNA obtained from mRNA from the salivary glands, producing a total of 81,178 sequences (reads) with an average size of 400.8 bases. Were assembled 4,558 contigs using the program Genomics CLC-(CLCBio) and annotated by software Blast2GO, based on sequence similarity. These were compared to various banks (GenBank, GO, Enzyme Codes, InterPro, KEGG). The results showed that 20.93% of them were classified as belonging to the secretory pathway and 14.77% as proteins of membrane, confirming the tissue of salivary gland. The main families of transcribed genes were lipocalins (15.6%), moubatins which can be sub-classes of lipocalins (6.23%), protein with a tail acid (1.63%), and metalloproteases (1.23%). The sequences of interest present in the salivary glands were cloned into bacterial heterologous system[3-5]. The recombinant proteins were expressed in sufficient quantities to analyze the sequences of lipocalins, moubatins, metalloproteases, cell cycle modulating and related to analgesia. All these proteins show functions that modify the coagulation activities, modulating the immune response and inhibition of platelet aggregation, among others, showing their potential for development of bioproducts with medical and industrial interests.