Journal of Clinical Infectious Diseases & Practice
Open Access

Neopterin was initial isolated from larvae of bees, in employee bees and in secretion in 1963, and later from human water by Sakurai and Goto in 1967. Nucleoside triphosphate via nucleoside triphosphate cyclohydrolase I by activated monocytes, macrophages, nerve fibre cells, and epithelium cells and to a lesser extent in nephritic animal tissue cells, fibroblasts, and tube sleek muscle cells upon stimulation primarily by antiviral gamma and to a lesser extent by antiviral alpha and beta with its unharness being increased by growth mortification issue [1]. GTPCH I RNA expression is synergistically and severally induced by antiviral gamma through the Jak2/Stat pathway of nuclear transcription regulation and thru TNF by the NF-kappa B pathway (Figure 1). unharness in response to cytokines free by T-lymphocytes Associate in Nursing natural killer cells create neopterin an indicator of activation of cell mediate immunity together with unharness by infections related to activation of T-lymphocytes and natural killer cells, malignancies, response diseases, rejection of transplanted organs, and arterial sclerosis. At its initial isolation within the Nineteen Sixties neopterin was detected within the pupae of bees by ion exchange action followed by chromatography. Within the seventies gas chromatographic-mass fragment graphic strategies were delineated permitting measuring in water [2]. Later detection and quantification of neopterin succeeded in blood serum, urine, and alternative body fluids victimization commonplace high and by reverse-phase superior liquid action with visible light detection. Later easier radioimmunoassays and a lot of recently protein connected immunosorbent assays are developed that area unit appropriate for giant numbers of samples. Semi quantitative measuring with gage system victimization polyclonal antineopterin antibodies has been valid and should be appropriate for side testing and within the setting of developing countries.

Figure 1: Pathways for induction of neopterin production.

Neopterin Unharness in Microorganism Infections

During acute microorganism infections enhanced neopterin levels are determined, that correlate with the activity of wellness. This was initial delineated in 1979 and later neopterin elevations were noted in infections with liver disease viruses, Epstein-Barr, Cytomegalo, measles, mumps, chickenpox herpes, rubella, and contagious disease viruses. Elevated neopterin levels in body fluids were found at the tip of the time period before the onset of clinical symptoms. the very best neopterin levels occur simply before specific antibodies against the virus become detectable, that is regarding 2 to four weeks once onset of enhanced neopterin production. In acute chickenpox herpes infection peak neopterin levels were determined at the tip of looks of the rash and in rubeola infection one to 3 days once appearance of the rash [3].

Protection with live viruses, for instance, measles, epidemic parotitis and epidemic roseola and virus immunizing agent, resulted in a very important increase of neopterin freelance of presence of any symptoms. In rubeola vaccination neopterin levels were determined to rise at a median of five days once vaccination regarding seven days before the looks of antibodies. These investigations purpose to a future application of measurements neopterin as a correlate of a fortunate vaccination. Neopterin ought to be investigated as a marker to guage protecting effectuality of vaccines stimulating cell mediate immunity against mycobacterial, parasitic, or microorganism diseases. The magnitude of the induced neopterin levels might be place into relationship to incidence of the unwellness immunised against the population of immunized kids [4]. Blood serum neopterin levels were additionally found to be considerably elevated in symptomatic virus infections with levels beyond in rubeola and contagious disease virus disease. Levels correlate with length of fever and severity of wellness. Investigations into the physiological functions of neopterin in microorganism infections disclosed that it's ready to delay the event of the cytopathic result of coxsackie B5 virus in Hep-2 cells. A projected mechanism is that the stimulation of inducible gas synthase expression resulting in a rise in gas production. Alternative mechanisms embrace the induction of the translocation of the nuclear factor-kappa B to the nucleus.

Neopterin as Surrogate Marker for Microorganism Load to Watch Response to Antiretroviral Treatment

In a very land mark study the consequences of twin polymerase substance (RT) medical care and extremely active antiretroviral medical care (HAART) on neopterin levels in patients with HIV infection were compared to HIV clean controls, HIV infected patients not on treatment, and patients WHO had stopped treatment. RT substance treatment weakened current levels of neopterin. Medication weakened neopterin levels considerably more. This confirmed results of a previous study on the consequences of medication on neopterin levels. Neopterin levels in patients WHO out of print medication became just like untreated HIV patients [5]. Neopterin is also significantly|a very} helpful surrogate marker for observance of management of HIV replication in settings in developing countries wherever HIV polymer microorganism load measuring isn't out there and should be a less expensive different particularly if semi quantitative dip stick tests area unit used for water samples. Longitudinal serial measurements within the same individual might overcome difficulties with interpretation in settings wherever chronic parasitic (malaria) or microorganism infections could elevate the baseline neopterin level and could allow monitoring of response to antiretroviral treatment in the absence of resistance testing and provide means to monitor compliance in the outpatient setting [6].

Neopterin Levels in Bacterial Infections

Patients with bacterial infections with species other than mycobacteria showed significantly lower urinary neopterin levels compared to patients with viral infections in one study but no statistically significant difference in a more recent study [7]. Within the group of bacterial infections it was shown that patients with symptoms for at least 5 days had significantly higher neopterin concentrations than patients with acute illness. This applied particularly to bacterial pneumonia. Patients with urinary tract infections were found to have similar levels to patients with viral infections with data on urinary neopterin concentrations but not serum concentrations.

Thus it remains unclear whether local production of neopterin takes place in urinary tract infections and serum neopterin would stay low. There was no significant difference in neopterin levels between patients with febrile neutropenia and underlying haematological and oncological conditions and gram-negative versus gram-positive infections [8]. In patients on an intensive care unit with sepsis and septic shock urinary neopterin/creatinine ratios were found to be significantly higher compared to patients with other forms of systemic inflammatory responses syndromes and serum neopterin levels were higher in nonsurvivors compared to survivors of sepsis and multiorgan failure scores correlated with neopterin levels. In this context it was however noted that neopterin levels correlated negatively with reduced renal function reflecting renal failure causing a reduced excretion of neopterin. Future studies could correct for reduced excretion due to reduced renal function by calculation of the serum neopterin/ creatinine ratio [9].

Investigations on critically ill patients on intensive care units evaluated neopterin levels as tool to discriminate patients with systemic inflammatory response syndrome with and without infectious etiology. Neopterin levels were found to have a specificity of 78% for discriminating infectious and noninfectious etiology of critical illness

Bacterial meningitis was associated with both elevated serum and CSF neopterin levels compared to controls. In Lyme neuroborreliosis-a late complication of infection by the tick-born spirochete Borrelia burgdorferi-high neopterin concentrations were found in CSF of patients, whereas serum neopterin levels were not markedly increased, confirming intrathecal neopterin production [10]. Infection with Treponema pallidum subsp. pallidum (syphilis) was not associated with elevated neopterin levels. In melioidosis by Pseudomonas pseudomallei neopterin concentrations were found to be significantly higher than controls.

Significance of Neopterin in Parasitic Infections

The first study of neopterin levels in parasitic infections included measurements of urinary neopterin by HPLC in patients with Plasmodium falciparum and vivax infections including patients with low grade parasitemia [11]. All patients had elevated urinary neopterin levels compared to uninfected controls to a level of 664 to 5189 micromol neopterin/mol creatinine. Levels in patients treated with quinine sulphate and levels in untreated patients were not significantly different [12]. A subsequent detailed interventional study provided data on urinary neopterin levels in volunteers experimentally infected with Plasmodium falciparum. Serial monitoring revealed that urinary neopterin levels were not elevated until peripheral blood parasite densities had increased through 3 to 4 cycles of intraerythrocytic schizogony. A sharp rise in urinary neopterin was detectable at the beginning of day 14 after infection. There was an increase one day after onset of fever. In one patient a urinary neopterin increase was noted without the occurrence of fever. Neopterin production in falciparum malaria seems to be a direct effect of plasmodial antigens on monocytes/ macrophages [13].

Conclusion

Neopterin is a nonspecific marker of activated cell mediated immunity involving release of interferon gamma. Neopterin may be a useful marker for more accurate estimation of extent of disease and hence prognosis. Knowledge of all potential causes of its elevation can overcome problems with reduced specificity in a patient known to have a specific infectious disease. Longitudinal serial measurements in the same individual could overcome difficulties with interpretation in settings where chronic parasitic or bacterial infections may elevate the baseline neopterin level and could allow monitoring of response to antiretroviral, antituberculous, and antiparasitic treatment in the absence of resistance testing and provide means to monitor compliance in the outpatient setting. This is particularly important in the current context of emerging multiple drug resistance of HIV and mycobacterium tuberculosis. Neopterin for which high quality ELISA systems to measure urine and blood levels are commercially available is an underused marker in clinical practice and is suitable for introduction into the routine clinical laboratory practice.

Conflict of Interest

The author declares that there is no conflict of interests regarding the publication of this paper.

1. Berdowska A, Zwirska-Korczala K (2001) Neopterin measurement in clinical diagnosis. J Clin Pharm Ther 26: 319–329.

Indexed at, Google Scholar , Crossref

2. Hoffmann G, Wirleitner B, Fuchs D (2003) Potential role of immune system activation-associated production of neopterin derivatives in humans. Inflamm Res 52: 313–321.

Indexed at, Google Scholar , Crossref

3. Huang A, Zhang YY, Chen K, Hatakeyama K, Keaney JF (2005) Cytokine-stimulated GTP cyclohydrolase I expression in endothelial cells requires coordinated activation of nuclear factor-𝜅b and Stat1/Stat3. Circu Res. 96: 164–171.

Indexed at, Google Scholar , Crossref

4. Buhrer-Sekula S, Hamerlinck FFV, Out TA, Bordewijk LG, Klatser PR, et al. (2000) Simple dipstick assay for semi-quantitative detection of neopterin in sera. J Immunol Methods. 238: 55–58.

Indexed at, Google Scholar , Crossref

5. Reibnegger G, Boonpucknavig V, Fuchs D, Hausen A, Schmutzhard E, et al. (1984) Urinary neopterin is elevated in patients with malaria. Trans R Soc Trop Med Hyg 78: 545–546.

Indexed at, Google Scholar , Crossref

6.  Reibnegger G, Auhuber I, Fuchs D (1988) Urinary neopterin levels in acute viral hepatitis. Hepatology. 8: 771– 774.

Indexed at, Google Scholar , Crossref

7.  Griffin DE, Ward BJ, Juaregui E, Johnson RT, Vaisberg A, et al. (1992) Immune activation during measles: beta 2- microglobulin in plasma and cerebrospinal fluid in complicated and uncomplicated disease. J Infect Dis 166: 1170–1173.

Indexed at, Google Scholar , Crossref

8.  Zaknun D, Weiss G, Glatzl J, Wachter H, Fuchs D (1993) Neopterin levels during acute rubella in children. Clin Infect Dis 17: 521–522.

Indexed at, Google Scholar , Crossref

9.  Fuchs D, Weiss G, Reibnegger G, Wachter H (1992) The role of neopterin as a monitor of cellular immune activation in transplantation, inflammatory, infectious, and malignant diseases. Crit Rev Clin Lab Sci 29: 307–341.

Indexed at, Google Scholar , Crossref

10. Chan CYP, Choi JWY, Cao KY (2006) Detection of serum neopterin for early assessment of dengue virus infection. J  Infect 53: 152–158.

Indexed at, Google Scholar , Crossref

11.  Babb K, Carrington CF, Monteil MA (1999) A preliminary study of neopterin as a potential marker for severe dengue virus infection. Trans R Soc Trop Med Hyg 93: 447–448.

Indexed at, Google Scholar , Crossref

12. Bratslavska O, Platace D, Mikla sevics E, Fuchs D, Martinsons MA (2007) Influence of neopterin and 7,8-dihydroneopterin on the replication of Coxsackie type B5 and influenza A viruses. Med Microb Immu196: 23–29.

Indexed at, Google Scholar , Crossref

13.  Nubling CM, Chudy M, Volkers P, ower JL (2006) Neopterin  levels during the early phase of human immunodeficiency virus, hepatitis C virus, or hepatitis B virus infection. Transfusion 46: 1886–1891.

Indexed at, Google Scholar , Crossref