Serum Cytokine Alterations Associated with Age of Patients with Nephropathia Epidemica

Abstract

Nephropathia epidemica (NE) is a zoonotic disease caused by hantaviruses transmitted from rodents, endemic in the Republic of Tatarstan, Russia. The disease presents clinically with mild, moderate, and severe forms, and time-dependent febrile, oliguric, and polyuric stages of the disease are also recognized. The patient’s cytokine responses have been suggested to play a central role in disease pathogenesis; however, little is known about the different patterns of cytokine expression in NE in cohorts of different ages and sexes. Serum samples and clinical records were collected from 139 patients and 57 controls (healthy donors) and were used to analyze 48 analytes with the Bio-Plex multiplex magnetic bead-based antibody detection kits. Principal component analysis of 137 patient and 55 controls (for which there was full data) identified two components that individually accounted for >15% of the total variance in results and together for 38% of the total variance. PC1 represented a proinflammatory TH17/TH2 cell antiviral cytokine profile and PC2 a more antiviral cytokine profile with patients tending to display one or the other of these. Severity of disease and stage of illness did not show any correlation with PC1 profiles; however, significant differences were seen in patients with high PC1 profiles vs. lower for a number of individual clinical parameters: High PC1 patients showed a reduced number of febrile days, but higher maximum urine output, higher creatinine levels, and lower platelet levels. Overall, the results of this study point towards a stronger proinflammatory profile occurring in younger NE patients, this being associated with markers of acute kidney injury and low levels of high-density cholesterol. This is consistent with previous work indicating that the pathology of NE is immune driven, with an inflammatory immune response being associated with disease and that this immune response is more extreme in younger patients.

Rosuvastatin as a Supplemental Treatment for the Clinical Symptoms of Nephropathia Epidemica: A Pilot Clinical Study

“…These findings suggest that including rosuvastatin as a supplementary treatment could improve NE symptoms. We believe that the effect of rosuvastatin was linked to its anti-inflammatory effects which have been demonstrated in vitro [ 32 ] and in vivo [ 33 , 34 ]. It has been suggested that the inhibitory effect of statins on inflammation is due to the reduced production of proinflammatory cytokines [ 32 , 35 ].…”

“…We believe that the effect of rosuvastatin was linked to its anti-inflammatory effects which have been demonstrated in vitro [ 32 ] and in vivo [ 33 , 34 ]. It has been suggested that the inhibitory effect of statins on inflammation is due to the reduced production of proinflammatory cytokines [ 32 , 35 ]. In this study, rosuvastatin reduced the serum levels of only a few proinflammatory cytokines, namely IL-1α, IL-1β, and IL-8.…”

Serum Markers Associated with Disease Severity in a Bosnian Hemorrhagic Fever with Renal Syndrome Cohort

“…This retrospective PUUV patient cohort study aimed to identify biomarkers associated with more severe disease in terms of platelet count and kidney injury. IL-18 is an important pro-inflammatory cytokine often found to be upregulated in PUUV patients compared to healthy controls, indicating a role in pathogenesis [ 12 , 13 , 14 , 15 ]. In the current study, IL-18 was significantly higher in patients in the low platelet group.…”

Neutrophil‐to‐lymphocyte ratio is elevated in acute hantavirus infection and correlates with markers of disease severity

“…Hantavirus infection induces a cytokine storm activating a plethora of immunopathological processes. Age‐ and gender‐dependent differences were described in the immune response against hantavirus infection 10–12 . Several cytokines and markers of cellular damage have been identified to be associated with severity of clinical course in hantavirus infection 7,13–23 …”

“…Age-and gender-dependent differences were described in the immune response against hantavirus infection. [10][11][12] Several cytokines and markers of cellular damage have been identified to be associated with severity of clinical course in hantavirus infection. 7,[13][14][15][16][17][18][19][20][21][22][23] The balanced host immune reaction determines the severity of disease by eradication of the invading pathogen but avoiding detrimental tissue damage due to poorly controlled immune activation.…”